Macrophage defect and inflammatory cell recruitment dysfunction in Salmonella susceptible C3H/HeJ mice

Weinstein, Debra L.; Lissner, C R; Swanson, R. N.; O'Brien, Alison D.

doi:10.1016/0008-8749(86)90326-6

Cited by 44 publications

(28 citation statements)

References 24 publications

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“…Therefore, infection created an increase in the relative amounts of MU in wild-type mice and, interestingly, of neutrophils in the absence of SHP-1. In comparison, LPS stimulation created the usual [27,28] strong increase in the percentage of neutrophils with a relatively low level of MU in both types of mice. As for absolute numbers at 3 and 6 h post inoculation, SHP-1-deficient mice had significantly more MU, neutrophils and eosinophils recruited in the pouch than their wild-type counterparts (Fig.…”

Section: Tnf-a and Mip-2 Expression In Leishmania Majorinfected Footpadsmentioning

confidence: 87%

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

et al. 2005

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Modulation of the phagocyte protein tyrosine phosphatase (PTP) SHP-1 by the parasite Leishmania favors its survival and propagation within its mammalian host. In vivo, the absence of SHP-1 leads to virtually absent footpad swelling, accompanied by enhanced inducible nitric oxide synthase expression. In this study, using an air pouch model, we show that viable motheaten SHP-1-deficient mice harbored a stronger inflammatory response against Leishmania infection than wild-type mice. This response was portrayed by higher pro-inflammatory cytokine (TNF-a, IL-1b and IL-6) expression and secretion and by greater chemokine and chemokine receptor expression. These inflammatory molecules were probably responsible for the stronger cellular recruitment, mainly of neutrophils, seen at the site of infection in viable motheaten mice within 6 h post inoculation. We also provide strong evidence that protein tyrosine phosphatases in general, and SHP-1 in particular, are important regulators of chemokine gene expression. Overall, this study suggests that the ability of Leishmania to induce SHP-1 activity in its host allows the taming of an otherwise strong innate inflammatory response that would be detrimental for its survival and progression.

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Section: Tnf-a and Mip-2 Expression In Leishmania Majorinfected Footpadsmentioning

confidence: 87%

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

et al. 2005

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“…Several studies have shown an enhanced sensitivity of TLR4-deficient C3H/HeJ mice when compared with C3H/HeN mice to a broad range of infectious models (35), including E. coli-induced pyelonephritis (36), Salmonella typhimurium, and Leishmania donovani (37). Subsequently, several groups demonstrated that the dramatic susceptibility of the C3H/ HeJ mice to Salmonella was due to a reduced recruitment of macrophages and an inherent activation defect in these cells (38,39,40,41). The increased susceptibility of C3H/HeJ mice to M.tb.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Expression Is Required to Control ChronicMycobacterium tuberculosisInfection in Mice

Abel

Thiéblemont

Quesniaux

et al. 2002

The Journal of Immunology

331

234

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Endotoxin from Gram-negative bacteria bound to CD14 signals through Toll-like receptor (TLR) 4, while components of Gram-positive bacteria, fungi, and Mycobacterium tuberculosis (M.tb.) preferentially use TLR2 signaling. We asked whether TLR4 plays any role in host resistance to M.tb. infection in vivo. Therefore, we infected the TLR4 mutant C3H/HeJ mice and their controls, C3H/HeN mice, with M.tb. by aerosol. TLR4 mutant mice had a reduced capacity to eliminate mycobacteria from the lungs, spread the infection to spleen and liver, with 10–100 times higher CFU organ levels than the wild-type mice and succumbed within 5–7 mo, whereas most of the wild-type mice controlled infection and survived the duration of the experiment. The lungs of TLR4 mutant mice showed chronic pneumonia with increased neutrophil infiltration, reduced macrophages recruitment, and abundant acid-fast bacilli. Furthermore, the pulmonary expression of TNF-α, IL-12p40, and monocyte chemoattractant protein 1 was significantly lower in C3H/HeJ mice when compared with the wild-type controls. C3H/HeJ-derived macrophages infected in vitro with M.tb. produced lower levels of TNF-α. Finally, the purified mycobacterial glycolipid, phosphatidylinositol mannosides, induced signaling in both a TLR2- and TLR4-dependent manner, thus suggesting that recognition of phosphatidylinositol mannosides in vivo may influence the development of protective immunity. In summary, macrophage recruitment and the proinflammatory response to M.tb. are impaired in TLR4 mutant mice, resulting in chronic infection with impaired elimination of mycobacteria. Therefore, TLR4 signaling is required to mount a protective response during chronic M.tb. infection.

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“…The P values for the comparisons are Ͻ0.0005 (one asterisk) and Ͻ0.0005 (two asterisks). cruitment (38,39,52). At the same time, Salmonella-dependent activation of macrophages for tumoricidal function and interleukin-6 production, Salmonella-induced dendritic cell maturation, and the development of anti-Salmonella adaptive immunity appear to be relatively unaffected in C3H/HeJ mice (10,25,44,46,56), indicating that there are TLR4-independent mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-Like Receptor 4 in Macrophage Activation and Tolerance duringSalmonella entericaSerovar Typhimurium Infection

Cherayil

2003

Infect Immun

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Toll-like receptors (TLRs) play an important role in the innate immune response, particularly in the initial interaction between the infecting microorganism and phagocytic cells, such as macrophages. We investigated the role of TLR4 during infection of primary murine peritoneal macrophages with Salmonella enterica serovar Typhimurium. We found that macrophages from the C3H/HeJ mouse strain, which carries a functionally inactive Tlr4 gene, exhibit marked impairment of tumor necrosis factor alpha (TNF-␣) secretion in response to S. enterica serovar Typhimurium infection. However, activation of extracellular growth factor-regulated kinase and NF-B signaling pathways was relatively unaffected, as was increased expression of TNF-␣ mRNA. Furthermore, macrophage tolerance, which is associated with increased expression of the NF-B p50 and p52 subunits, was induced by S. enterica serovar Typhimurium even in the absence of functional TLR4. These results indicate that during infection of macrophages by S. enterica serovar Typhimurium, TLR4 signals are required at a posttranscriptional step to maximize secretion of TNF-␣. Signals delivered by pattern recognition receptors other than TLR4 are sufficient for the increased expression of the TNF-␣ transcript and at least some genes associated with macrophage tolerance.

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Macrophage defect and inflammatory cell recruitment dysfunction in Salmonella susceptible C3H/HeJ mice

Cited by 44 publications

References 24 publications

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

Toll-Like Receptor 4 Expression Is Required to Control ChronicMycobacterium tuberculosisInfection in Mice

Role of Toll-Like Receptor 4 in Macrophage Activation and Tolerance duringSalmonella entericaSerovar Typhimurium Infection

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