Interferon gamma (IFN-γ) production by gut-associated lymphoid tissue and spleen following oral Salmonella typhimurium challenge

Ramarathinam, Lakshmi; Shaban, Radwan A.; Niesel, David W.; Klimpel, Gary R.

doi:10.1016/0882-4010(91)90020-b

Cited by 66 publications

(53 citation statements)

References 29 publications

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“…IFN-␥ plays a critical role in stimulation of Th1 immune responses and the clearance of intracellular pathogens, such as Salmonella (12,17,34,37). High IFN-␥ levels were previously reported during early Salmonella infection (42), as also noted in this study. Cytokine profiling for the presence of Th1 and Th2 cytokines in sera from WT S. enterica serovar Typhimurium-infected mice indicated increased IFN-␥ levels and no detectable levels of IL-2 and IL-4, confirming the involvement of Th1 responses during salmonellosis (data not shown).…”

Section: Fig 9 Levels Of Tnf-␣ (A) Kc (B)supporting

confidence: 68%

Murein Lipoprotein Is a Critical Outer Membrane Component Involved inSalmonella entericaSerovar Typhimurium Systemic Infection

Fadl¹,

Sha²,

Klimpel³

et al. 2005

Infect Immun

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Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two-to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5-to 10-fold-higher levels of tumor necrosis factor-␣ and IL-6; the levels of these cytokines were 1.7-to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased susceptibility to death. Since the lpp DKO mutant retained intact LPS, we constructed an S. enterica serovar Typhimurium tripleknockout (TKO) mutant in which the lppA and lppB genes were deleted from an existing msbB mutant (msbB encodes an enzyme required for the acylation of lipid A). Compared to the lpp DKO and msbB SKO mutants, the lpp-msbB TKO mutant was unable to induce cytotoxicity and to produce cytokines and chemokines in vitro and in vivo. These studies provided the first evidence of the relative contributions of Lpp and lipid A acylation to Salmonella pathogenesis.

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Section: Fig 9 Levels Of Tnf-␣ (A) Kc (B)supporting

confidence: 68%

Murein Lipoprotein Is a Critical Outer Membrane Component Involved inSalmonella entericaSerovar Typhimurium Systemic Infection

Fadl¹,

Sha²,

Klimpel³

et al. 2005

Infect Immun

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“…In contrast, mice infected with SL1344 and RVY-5 displayed a differential IFN-␥ response. As previously reported (19,30), SL1344-infected mice showed steadily increasing levels of IFN-␥ until the deaths of the animals occurred (days 7 and 11). Interestingly, mice infected with RVY-5 showed IFN-␥ levels significantly higher than those of serum from SL1344-infected mice (day 7), even though the bacterial load of RVY-5 was 100-to 1,000-fold lower than that of SL1344.…”

supporting

confidence: 53%

mig-14Is a Horizontally Acquired, Host-Induced Gene Required forSalmonella entericaLethal Infection in the Murine Model of Typhoid Fever

et al. 2000

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We have characterized a host-induced virulence gene, mig-14, that is required for fatal infection in the mouse model of enteric fever. mig-14 is present in all Salmonella enterica subspecies I serovars and maps to a region of the chromosome that appears to have been acquired by horizontal transmission. A mig-14 mutant replicated in host tissues early after infection but was later cleared from the spleens and livers of infected animals. Bacterial clearance by the host occurred concomitantly with an increase in gamma interferon levels and recruitment of macrophages, but few neutrophils, to the infection foci. We hypothesize that the mig-14 gene product may repress immune system functions by interfering with normal cytokine expression in response to bacterial infections.There are six subspecies of Salmonella enterica that are capable of colonizing both warm-and cold-blooded animals (1, 9). S. enterica subspecies I serovars are strictly associated with infection of warm-blooded animals and can cause a wide a range of diseases, including gastroenteritis, bacteremia, and typhoid fever (11). S. enterica serovar Typhimurium (from here on referred to as serovar Typhimurium) is the causative agent of gastroenteritis in humans and a typhoid-like disease in mice (11). Serovar Typhimurium survives and replicates within phagocytic cells of the reticuloendothelial system, resulting in the release of proinflammatory cytokines in response to bacterial compounds such as lipopolysaccharide (LPS) and peptidoglycan (11,16,17,20). Two of these inflammatory cytokines, tumor necrosis factor alpha (TNF-␣) and gamma interferon (IFN-␥), are required for host clearance of Salmonella infections (11,12,16,18). Treatment of infected animals with IFN-␥ decreases the numbers of bacteria found in the spleen early in infection, and injection of anti-TNF-␣ or anti-IFN-␥ abolishes the ability of mice to clear sublethal doses of serovar Typhimurium (12,26,27). Recently, it has been reported that modified Salmonella lipid A (an LPS component) can reduce the LPS-mediated expression of TNF-␣ by human monocytes and E-selectin by endothelial cells (14). These lipid A modifications are regulated by the PhoP/PhoQ virulence regulon (7, 13), suggesting a potential role for PhoP/PhoQ-activated genes not only in intracellular survival but also in lowering cytokine and chemokine production.In the present study we characterized the virulence properties and evolutionary history of a host-induced serovar Typhimurium factor with potential immunomodulatory functions. A previous study described a PhoP/PhoQ-dependent, macrophage-inducible promoter, fmi-14, which exhibited a 22-fold induction within murine macrophages (36). To identify the open reading frame (ORF) associated with fmi-14, we isolated an adjacent 2.2-kb serovar Typhimurium DNA fragment by recombinational cloning (6). Sequence analysis of this fragment revealed a single ORF (mig-14) encoding a putative 298-amino-acid (aa) soluble polypeptide with limited homology to Bacillus subtilis RecG, an ATP-dependen...

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“…As a consequence, mechanisms that activate macrophages are necessary to control S. typhimurium. The importance of macrophage activation is emphasized by the high susceptibility to S. typhimurium of mice deficient in IFN-␥ receptor or of mice in which IFN-␥ or TNF-␣ are neutralized with specific Abs (15,19,39,40). Both IFN-␥ and TNF-␣ are crucial for macrophage activation.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Role of B Lymphocytes in Protective Immunity AgainstSalmonella typhimuriumInfection

Mittrücker

Raupach

Köhler

et al. 2000

The Journal of Immunology

180

154

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Infection of mice with Salmonella typhimurium gives rise to a disease similar to human typhoid fever caused by S. typhi. Since S. typhimurium is a facultative intracellular bacterium, the requirement of B cells in the immune response against S. typhimurium is a longstanding matter of debate. By infecting mice on a susceptible background and deficient in B cells (Igμ−/− mice) with different strains of S. typhimurium, we could for the first time formally clarify the role of B cells in the response against S. typhimurium. Compared with Igμ+/+ mice, LD50 values in Igμ−/− mice were reduced during primary, and particularly secondary, oral infection with virulent S. typhimurium. After systemic infection, Igμ−/− mice cleared attenuated aroA− S. typhimurium, but vaccine-induced protection against systemic infection with virulent S. typhimurium involved both B cell-dependent and -independent effector mechanisms. Thus, B cell-mediated immunity plays a distinct role in control of S. typhimurium in susceptible mice.

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Interferon gamma (IFN-γ) production by gut-associated lymphoid tissue and spleen following oral Salmonella typhimurium challenge

Cited by 66 publications

References 29 publications

Murein Lipoprotein Is a Critical Outer Membrane Component Involved inSalmonella entericaSerovar Typhimurium Systemic Infection

Murein Lipoprotein Is a Critical Outer Membrane Component Involved inSalmonella entericaSerovar Typhimurium Systemic Infection

mig-14Is a Horizontally Acquired, Host-Induced Gene Required forSalmonella entericaLethal Infection in the Murine Model of Typhoid Fever

Cutting Edge: Role of B Lymphocytes in Protective Immunity AgainstSalmonella typhimuriumInfection

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