ARTICULO MEDICO: PATOGENESIS DE GASTROENTERITIS POR SALMONELA

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Pathogenesis of Salmonella gastroenteritis
Authors
Camille N Kotton, MD
Elizabeth L Hohmann, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Elinor L Baron, MD, DTMH
Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2013. | This topic last updated: may 1, 2012.
INTRODUCTION — Salmonellae cause a broad range of infections, including gastroenteritis,
enteric fever, bacteremia, endovascular infections, and focal infections such as osteomyelitis and
abscesses. Salmonellae are facultative anaerobic gram-negative bacilli and usually enter the body
via the gastrointestinal (GI) tract, where they can persist for long periods of time. Salmonellae can
act as both commensals and pathogens and are found in the GI tracts of domestic and wild
animals, including insects, reptiles, birds, and mammals.
Although there are many types of Salmonella, they can be divided into two broad categories: those
that cause typhoid and enteric fever and those that primarily induce gastroenteritis:
· The typhoidal Salmonella, such as S. typhi or S. paratyphi primarily colonize humans, are
transmitted via the consumption of fecally contaminated food or water, and cause a
systemic illness usually with little or no diarrhea. (See "Epidemiology, microbiology, clinical
manifestations, and diagnosis of typhoid fever".)
· The much broader group of nontyphoidal Salmonella usually results from improperly
handled food that has been contaminated by animal or human fecal material. It can also be
acquired via the fecal-oral route, either from other humans or farm or pet animals [1].
(See "Microbiology and epidemiology of salmonellosis".)
The bacterial and host factors that contribute to Salmonella gastroenteritis will be reviewed here
(figure 1).




FIG. 1.Pathogenic bacterial properties and host factors conferring increased susceptibility to Salmonella infection

The approach to patients with Salmonella in a stool culture is discussed separately.
(See "Approach to the patient with nontyphoidal Salmonella in a stool culture".)
GENERAL ISSUES — A number of different serovars of Salmonella cause human infection. The
source of infection typically is from food.
Serotypes — The 2000-plus serovars of Salmonella can be characterized by three major antigens:
the somatic O antigen, which is derived from the LPS cell wall component; the flagellar H antigen,
and the surface Vi antigen. The O-antigen is widely used by clinical laboratories to divide
Salmonella into serogroups A, B, C1, C2, D, and E (table 1).

Salmonella serogroups: Examples of important specific serotypes and their characteristic clinical infections

Serogroup	Example (serotype)*	Characteristic syndrome
A	S. paratyphi A	Enteric fever
B	S. paratyphi B	Enteric fever or gastroenteritis
B	S. typhimurium	Gastroenteritis
B	S. heidelberg	Gastroenteritis, bacteremia
C	S. paratyphi C	Enteric fever
C	S. choleraesuis	Bacteremia
C	S. newport	Gastroenteritis
D	S. typhi	Enteric fever
D	S. enteritidis	Gastroenteritis
D	S. dublin	Bacteremia

* All listed serotypes are formally members of the species Salmonella enterica, subspecies enterica. There are many additional serotypes of Salmonellae that are named after geographical locales: S. javiana, S. tennessee, S. cubana, etc. Chronic biliary carriage occurs almost exclusively with S. typhi or S. paratyphi.

 Significant cross-reactivity can occur between serogroups. The serogroups cannot be used to divide enteric fever-causing strains from
gastroenteritis-causing strains: group D contains both S. enteritidis and S. typhi, while group B
contains S. typhimurium as well as some strains of S. paratyphi. To investigate a possible outbreak,
further identification must be done with bacteriophage typing, restriction fragment length
polymorphism analysis, pulsed-field gel electrophoresis, and plasmid profile determination.
The host specificity of different Salmonella serotypes often determines the nature of the clinical
illness. Classic typhoid or enteric fever is caused by Salmonella typhi and Salmonella paratyphi.
These strains are highly adapted for humans and do not colonize or cause disease in animals,
though S. paratyphi has very rarely been associated with domestic animals. (See "Pathogenesis of
typhoid fever".) Those serotypes which cause enteric fever are frequently not associated with
significant diarrheal symptoms, although enteric fever may be heralded by transient diarrhea prior to
the onset of fever.
Salmonella enteritidis and Salmonella typhimurium have broad host ranges and may produce
colonization or gastroenteritis in humans, mice, and fowl. (See "Microbiology and epidemiology of
salmonellosis".) These serotypes are most frequently associated with gastroenteritis in humans
because of the large reservoirs of bacteria in domestic animals. Salmonella choleraesuis (adapted
for swine) and Salmonella dublin (adapted for cattle) are associated with human septicemia and
metastatic foci of infection but are uncommon causes of gastroenteritis [2]. Salmonella gallinarumpullorum
(adapted for fowl) causes relatively transient illness in humans only after very large inocula
are ingested. The molecular bases of these species specificities is complex and currently under
investigation.
The epidemiology of Salmonella has evolved over time. During the 2000s, the incidence of
Salmonella typhimurium decreased, while serotypes Newport, Mississippi, and Javiana increased in
incidence. Specific control programs focusing on contaminated eggs might have led to the reduction
of S. enteritidis infections. Rates of antibiotic resistance among several serotypes have been
increasing and are an area of significant concern; a substantial proportion of S. typhimurium and S.
newport isolates are multi-drug resistant [3].
Sources of infection — There are an estimated two to four million cases of Salmonellosis per year
in the United States, with gastroenteritis as the most common clinical presentation. Nontyphoidal
Salmonella account for 9.7 percent of all bacterial foodborne illnesses and 30.6 percent of deaths
as of 1999 [4]; between the time periods 1996 to 1998 and 2005, the number of Salmonella cases
decreased by 9 percent [5]. Salmonella gastroenteritis usually results from improperly handled food.
It can also be acquired via the fecal-oral route, either from other humans or farm or pet animals.
(See "Differential diagnosis of microbial foodborne disease".) In the United States, serotypes
Typhimurium, Enteritidis, and Newport are the most common serotypes. During 2006, large
multistate outbreaks of Salmonellosis were linked to consumption of tomatoes, fruit salad, pet
turtles, and peanut butter [3].
It is estimated that 1 in 10,000 egg yolks is infected with Salmonella enteritidis. In 1976, there were
0.6 cases of Salmonella enteritidis per 100,000; by 1996 there were 3.6 cases per 100,000, with the
majority of the increase due to eggs. A recent risk assessment model for Salmonella enteritidis
infection in eggs estimates that of the approximately 69 billion eggs produced annually, 2.3 million
would be contaminated with Salmonella enteritidis and that an average of 661,633 human illnesses
would develop from their consumption [6]. An estimated 94 percent of these cases recover without
medical care, 5 percent visit a physician, an additional 0.5 percent are hospitalized, and 0.05
percent result in death.
A multistate outbreak of S. newport from imported mangos was felt to be related to hot water
treatment of the fruit to prevent importation of the Mediterranean fruit fly [7]. While fruit skin usually
acts as a physical barrier to pathogens, the heating and cooling of the fruit may have created an
inward hydrostatic force that allowed for the entry of S. newport. There have been numerous other
outbreaks, some of which are discussed separately. (See "Microbiology and epidemiology of
salmonellosis".) The incidence of salmonellosis is highest during the summer in temperate climates
(eg, from May to October in the Northern hemisphere) and during the rainy season in tropical
climates, which coincides with the peak in foodborne outbreaks.
Exotic pets may be a source of salmonellosis. Approximately 90 percent of reptiles carry
Salmonella. Cases of salmonellosis in infants have been reported in households in which iguanas,
bearded dragons, or snakes were handled by adults with probable subsequent spread to the
children [8]. An estimated 3 to 5 percent of all cases of salmonellosis in humans is due to exposure
to pets, including turtles, birds, rodents, dogs, and cats. (See "Zoonoses from dogs" and "Zoonoses
from cats" and "Zoonoses from pets other than dogs and cats".)
Infectious dose — Data on the number of Salmonella organisms required for clinical illness have
been obtained from studies on human volunteers and outbreaks in which the vehicle of inoculation
was quantitatively cultured [9]. Several general statements about infectious doses can be made:
· Large inocula (>10(4)) produce higher rates of illness after shorter incubation periods than
small inocula (≤10(3)).
· Asymptomatic excretion may occur after ingestion of small inocula, although even very
small inocula (5 to 100 organisms) may cause disease in susceptible hosts.
· Antibiotic use can reduce the infectious dose necessary to cause disease by diminishing
the normally protective indigenous flora (see below).
· The infectious dose is lower in patients with clinical conditions associated with a reduction
in gastric acidity such as neonates [10], achlorhydric states [11], gastric surgery [12,13] and
the use of antacids or H2 blockers [13,14].
· Water supplies are contaminated at lower levels than food, resulting in lower attack rates
and longer incubation periods in waterborne outbreaks.
· Salmonella may persist for months in cheese, frozen meat, or ice cream.
PATHOGENESIS — A number of factors related both to the pathogen and the host influence the
pathogenesis of Salmonella gastroenteritis.
Interaction of Salmonellae with enteric host defenses — Ingested microorganisms must
traverse the acidic barrier of the stomach in order to establish enteric infection (table 2).

 TABLE 2. Host factors that predispose to severe Salmonella infection

Impaired cell-mediated immunity

AIDS

Use of corticosteroids or other immunomodulatory agents

Malignancy

Impaired phagocytic function

Hemoglobinopathies

Chronic granulomatous disease

Malaria

Histoplasmosis

Schistosomiasis

Extremes of age

Neonates

Elderly

Decreased gastric acidity

Antacids or suppression of acid secretion

Achlorhydria

Altered intestinal function

Inflammatory bowel disease

Prior antibiotic therapy

Although Salmonella and other enteric pathogens survive poorly at the very low pH encountered in the stomach, Salmonella exhibit increased tolerance to "acid shock" if first exposed to a moderately
acidic environment (pH 4 to 5). The organism's ability to adapt to low pH has been called the acid
tolerance response [15].
Salmonellae that survive passage through the stomach must then compete with the normal
intestinal microbial flora. The indigenous flora is an important but often overlooked barrier to
infection with enteric pathogens. Elegant mouse studies performed in the 1960s showed that a
single injection of streptomycin reduced the oral infectious dose of Salmonella typhimurium by over
100,000-fold [16]. Studies in animals have shown that the protective effect of indigenous microbes
is due to a variety of factors including competition for nutrients, maintenance of a low luminal pH,
and production of inhibitory compounds such as volatile fatty acids [17,18].
These findings appear to be applicable to humans, as can be illustrated by the following
observations:
· Prophylactic antimicrobial therapy increases the frequency of salmonellosis among
travelers [19].
· Patients found to be infected during an outbreak of multidrug resistant Salmonella
typhimurium enteritis used antimicrobials in the month before the onset of illness much
more frequently than controls (30 versus 6 percent) [20]. A similar association with prior
antimicrobial use was noted in a multistate outbreak of illness caused by Salmonella
havana which was pansensitive to antimicrobial agents (30 versus 13 percent) [21]. The
association persisted even when controlled for the presence of underlying illness or
immunosuppression.
S. Typhimurium has a marked and unique growth advantage over other bacteria when using a
specific nutrient, ethanolamine, which is released from host tissue in the lumen of the inflamed
intestine and is not utilizable by competing bacteria [22]. Thus, by inducing intestinal inflammation,
S. Typhimurium sidesteps nutritional competition and creates a significant survival advantage for
itself.
In addition to competition from the indigenous bacterial flora, Salmonella must withstand a gamut of
enteric defenses including bile salts, pancreatic enzymes, Paneth cell antimicrobial peptides [23],
and secretory IgA [24].
Mechanisms of adherence and invasion — There are two main components to Salmonella
infection of the GI tract: adherence and subsequent invasion. Adherence is complex and is
mediated by multiple genes. Fimbriae are very important in adhering to and adapting to a eukaryotic
cell surface [25]; several fimbrial operons may facilitate adherence [26]. Biofilms may play a role as
well [25]. The invasion operon (inv) can also induce adherence [27].
Invasion may be achieved by several different mechanisms:
· Salmonella can selectively attach to specialized epithelial cells overlying Peyer's patches in
the colon known as M (microfold) cells. These cells are an important portal of entry of
Salmonellae and other pathogens into the submucosal lymphoid system [28]. M cells are
highly endocytic and can rapidly transfer material from their luminal side to their basal side,
where the T cells and antigen-presenting cells reside, ready to elicit an immune response.
· It has been suggested that the cells of the columnar epithelium may also be an important
common portal of entry for Salmonella, particularly since they greatly outnumber the M cells
[29].
· Salmonellae can also induce nonphagocytic cells such as enterocytes to internalize them.
This process of bacterial-mediated endocytosis has been extensively studied in vitro and
appears to be important in the pathogenesis of Salmonella gastroenteritis [30,31].
· Invasion can also occur via the dendritic cells that intercalate between epithelial cells by
extending protrusions into the gut lumen.
· Numerous small foci of solitary intestinal lymphoid tissues (SILTs) with a strong
inflammatory response can be found in the murine small intestine; Salmonella can be
observed within these SILTs at early stages of infection, and the SILTs may act as portals of
entry [32].
Following invasion into the cell, the bacteria remain within a modified phagosome known as the
Salmonella-containing vacuole (SCV), within which they will survive and replicate. Type III secretion
systems are used to translocate bacterial effector proteins into the host cell, mediating both invasion
and vacuole biogenesis. Vacuole biogenesis is a complex and dynamic process involving extensive
membrane remodeling, interactions with the endolysosomal pathway, actin rearrangements, and
microtubule-based movement and tubule extension [33].
The mechanisms of persistent Salmonella fecal shedding of Salmonella are under investigation.
The shdA gene, which encodes an outer membrane autotransporter protein that binds fibronectin, is
required for persistent shedding of Salmonella typhimurium in mice [34]. This raises the question of
whether this locus might mediate adherence of Salmonella at other clinically important structures
known to be foci of metastatic infection, such as arteries and bone.
Pathogenicity islands — Two Salmonella "pathogenicity islands" (SPI) have been found, termed
SPI-1 and 2, each about 40 kilobases of DNA and located at centrosomes 63 and 30 of the
chromosome, respectively [35-40]. Both SPIs encode multiple virulence factors, including Type III
secretions systems (TTSS). The TTSS creates a hypodermic needle-like apparatus (figure 2) and
injects proteins into the cells, facilitating uptake of the bacteria into those cells. SPI-1 encodes
genes needed for nonphagocytic cell invasion via a ruffling mechanism and initiation of intestinal
secretory and inflammatory responses. SPI-2 is induced within the cell and contains genes needed
for survival and replication within macrophages [41].

FIG. 2.Salmonella type III secretion system


Some of these genes induce secretory and inflammatory responses [42,43].Some of these genes on SPI-1 encode proteins homologous to Shigella proteins which direct the export and translocation of signaling molecules capable ofinteracting with eukaryotic cells [35,36]. The secreted proteins of both Salmonella and Shigella induce ruffled projections in eukaryotic cell membranes which subsequently invaginate and internalize the invading bacterium within a membrane bound vacuole, called macropinocytosis [44].
Mutants lacking these genes display reduced virulence. In one study avirulent environmental
isolates of S. senftenberg and S. litchfield contained deletions in SPI-1, while clinical isolates of the
same serotypes retained the gene cluster [45].
Inflammatory response mechanisms — In addition to facilitating their own uptake, virulent strains
of Salmonella are able to induce migration of subepithelial neutrophils across polarized epithelial
cells in vitro [46]. A substantial neutrophil infiltration into the intestine occurs in Salmonella
typhimurium-induced colitis in humans; whether this is due to effectors from Salmonella or innate
pathways of inflammation triggered by pathogen recognition receptors on cells in the lamina propria
is a matter of debate [47]. The paracellular traffic of neutrophils has been hypothesized to induce
diarrhea by causing paracellular fluid and electrolyte fluxes. This theory is supported by the
observation that strains which do not usually cause enteritis, such as S. typhi and S. gallinarum,
also do not induce neutrophil transmigration [48].
In addition to IL-8, Salmonella induce other proinflammatory cytokines such as GM-CSF, monocyte
chemotactic protein-1, and tumor necrosis factor-alpha in colonic epithelial cells, which in turn
mediate further immune responses [49]. Macrophages respond to S. typhimurium infection via
flagellin-mediated activation of Ipaf, a NACHT-leucine-rich repeat family member that activates
caspase-1 [50]. Activated caspase-1 is required for the secretion of proinflammatory cytokines, such
as interleukin (IL)-1beta and IL-18, and is important in host defense against a variety of pathogens;
caspase-1-deficient mice are more susceptible to several pathogens including, Shigella, Listeria
and Francisella tularensis [51-53], as well as Salmonella [54].
Lipid A is the biologically active component of lipopolysaccharide (LPS) found in the cell wall of
Salmonella and other gram-negative bacteria. Lipid A is toxic to mammalian cells and is a potent
immunomodulator. Certain features of the lipid A in Salmonella may correlate with virulence or with
activation of host inflammation [55,56]. Lipid A induces toll-like receptor 4 (TLR4)-mediated
responses, which are important for host defense against Salmonella infection, and modifications in
lipid A as part of Salmonella's adaptation to host environments reduce this signaling [57]. Death in
mice from Salmonella may be related to the toxic effect of lipid A, which triggers further production
of TNF-alpha and IL-1 beta. S. typhimurium mutants with a defective lipid A molecule have greatly
attenuated virulence in mice [58]. Structural modifications of lipid A are influenced by the Salmonella
virulence regulatory locus (phoP/phoQ) which responds to a variety of host intracellular
environmental signals [59]. For example, antimicrobial peptides have been shown to be part of the
first step in signal transduction across the bacterial membrane, resulting in activation of phoQ and
promotion of bacterial virulence [60]. PhoP has also been found to bind a promoter region of a drug
efflux system, thus connecting virulence with possible drug resistance [61].
Enterotoxins may also play a role in Salmonella gastroenteritis. An enterotoxin, encoded by the stn
gene and antigenically similar to cholera toxin has been identified [62-64]. While many Salmonellae
carry the stn gene, only a fraction express the gene, as assessed by CHO cell assay [65]. Additional
characterization of the enterotoxin is needed to assess its role in human pathogenesis.
Survival within phagocytes — Salmonellae have long been known to persist within the
reticuloendothelial system. Macrophages may be the main cell type to support bacterial growth in
vivo, and this growth is regulated by both the host and the Salmonella [66]. The ability of Salmonella
to survive within macrophages contributes to the dissemination of the microorganism from the
submucosa to the circulation and the reticuloendothelial system. Intracellular bacterial growth within
phagocytes is limited by mechanisms requiring reactive oxygen intermediates, reactive nitrogen
intermediates, lysosomal enzymes, and defensins. Both the phoP/phoQ virulence regulatory locus
[67-69] and the SPI-2 contain genes that are important for survival within macrophages. The
importance of this process is illustrated by studies that showed that phoP/phoQ-deleted S.
typhimurium, when used as a vaccine vector, caused no bacteremia or late sequelae in a limited
number of subjects who received a large oral inoculum [70]. Isolates of Salmonella typhimurium that
are unable to survive within macrophages in vitro are avirulent in mice [71].
Role of virulence plasmids — Nontyphoidal Salmonellae also carry a variety of virulence plasmids
[72]. A highly conserved 8 kilobase region of DNA contained within these plasmids has been
associated with the ability of strains to induce bacteremia and persist within the reticuloendothelial
system [72,73]. S. typhimurium has a self-transmissible [74] 90 kilobase virulence plasmid that
contains the genes spvRABCD and while it increases the growth rate of Salmonellae in
macrophages, it may have a limited contribution to virulence [75]. The virulence plasmid stimulates
IL-12 production in a mouse model, which may lead to attenuated T cell proliferation [76].
Immune response to Salmonella infection — Because of the frequency and nonspecific nature of
the symptoms of Salmonella gastroenteritis, little is known about the rates of reinfection and
correlates of immunity. The innate immune system, cell-mediated immunity, and humoral immunity
all play important roles in limiting Salmonella infection.
Innate immune system — The innate immune system plays a critical role in the initial response to
Salmonella infection. It may be the determining factor in whether the infection is subclinical or more
aggressive. The importance of macrophages and polymorphonuclear (PMN) leukocyte response to
Salmonella has been well described. Neutropenic mice have a high mortality in experimental
Salmonella infection [77], and depressed PMN function increases the incidence of Salmonella
infection in humans. These conditions most commonly include sickle cell anemia [78], malaria
[79,80], schistosomiasis [81], and histoplasmosis [82]. In addition, Toll receptor agonists such as
LPS, lipoprotein, and flagellin stimulate proinflammatory cytokine production, resulting in TNF-alpha
and interleukin responses [29]. Activation of Toll-like receptor 5 and Ipaf by Salmonella flagellin has
been a significant finding [83].
Cell-mediated immunity — Cell-mediated immunity plays an important role in clearing infection
and protecting against subsequent Salmonella infection. Clinical vigilance in the diagnosis and
management of Salmonella infections should be increased in settings associated with cellular
immunosuppression. As an example, infection is more severe and prolonged in patients with
depressed cellular immunity due to glucocorticoids [84], AIDS [85-87], and malignancy [88]. In one
study, nontyphoidal Salmonella (14 percent) were the second most frequent bacterial isolate after
Staphylococcus aureus (29 percent) in a study of 249 bacteremias in HIV-infected individuals [89].
Nude mice and mice deficient in alpha-beta T cells are more susceptible to Salmonella infections.
Murine models suggest that CD4+ T cells are more contributory than CD8+ T cells [29].
Humoral immune responses — The humoral response to Salmonella infection is complex and
may be protective or maladaptive. Its importance in containing Salmonella infection is illustrated by
the protective immunity induced in vaccination studies with S. typhi. Mice deficient in B cells due to
a targeted deletion of the Ig-mu gene show increased susceptibility to Salmonella infection and are
unable to mount a significant convalescent immune response [90]. In addition, mucosal humoral
immune responses may play a contributory role. Murine studies have shown that secretion of large
amounts of a single monoclonal IgA directed against Salmonella typhimurium lipopolysaccharide
(LPS) into the intestinal lumen provides significant protection against systemic disease [36].
Furthermore, mucosal antibodies to nontyphoidal Salmonellae appear to inhibit the "take" of the oral
live attenuated typhoid fever vaccine Ty21a [91].
However, in a study that evaluated the effect of serum from HIV-infected patients on the killing of S.
typhimurium in vitro, a high serum concentration of antibodies against the LPS of non-typhoidal
Salmonellae paradoxically prevented the destruction of Salmonella [92]. The authors postulated that
inhibitory antibodies in the serum of HIV-infected individuals could be responsible for this effect by
blocking the action of bactericidal antibodies. These results suggest that the preferred vaccine
target should be the bacterial outer-membrane proteins of non-typhoidal Salmonellae as opposed to
LPS, since LPS could potentially elicit inhibitory rather than the desired bactericidal antibodies.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The
Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on “patient info” and the keyword(s) of interest.)
· Basics topics (see "Patient information: Salmonellosis (Salmonella) (The Basics)")
SUMMARY
· The 2000-plus serovars of Salmonella can be characterized by three major antigens: the
somatic O antigen, which is derived from the lipopolysaccharide cell wall component, the
flagellar H antigen, and the surface Vi antigen. (See 'Serotypes' above.)
· The size of the inoculum is proportional to the frequency and rapidity of disease onset, but
even small inocula can cause disease. Enteric host factors that defend against Salmonella
infection include the acidic environment of the stomach and the normal intestinal microbial
flora. The infectious dose necessary to cause disease can be lower in settings of antibiotic
use and reduction of gastric acid. (See'Infectious dose' above and 'Interaction of
Salmonellae with enteric host defenses' above.)
· Salmonellae adhere to and invade the gastrointestinal tract and submucosal lymphoid
system through several different mechanisms. Bacterial entry into and survival within host
cells are facilitated by multiple virulence factors. (See 'Mechanisms of adherence and
invasion' above and 'Pathogenicity islands' above.)
· The ability of Salmonella to survive within macrophages contributes to the dissemination of
the microorganism from the submucosa to the circulation and the reticuloendothelial
system. (See 'Survival within phagocytes' above.)
· Virulent strains of Salmonella induce multiple host inflammatory responses and cytokines.
This is in part mediated by lipid A, a component of lipopolysaccharide in the cell wall.
(See 'Inflammatory response mechanisms' above.)
· The host innate immune response may determine whether Salmonella infection is
subclinical or more aggressive. Adaptive cell-mediated immunity plays an important role in
clearing and protecting against subsequent infection. The humoral response is complex and
may be protective or maladaptive. (See 'Immune response to Salmonella infection' above.)
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