Some Physiopathological Parameters of Natural Resistance to Infection in Murine Salmonellosis

Böhme, Diethelm; Schneider, Howard A.; Lee, Johanna M.

doi:10.1084/jem.110.1.9

Cited by 31 publications

(7 citation statements)

References 17 publications

(21 reference statements)

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“…As reported before [23], [24], S. typhimurium induced symptoms of septic shock in mice that started 2 h after intraperitoneal injection of 10 5 CFU and were initially characterized by piloerection, decrease in feeding and water consumption and general malaise. At later times, signs progressed to severe wasting and cachectia, with death before 5 days.…”

Section: Resultssupporting

confidence: 59%

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

et al. 2007

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BackgroundTo unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity.Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice.Conclusion/SignificanceWe propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections.

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Section: Resultssupporting

confidence: 59%

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

et al. 2007

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“…This would add another parameter to those described by previous authors, when studying differences in the susceptibility to infection. Thus, inbred strains of mice have been found to differ in their reticuloendothelial system function and differential leukocyte count (5), in the number or activity of their macrophages (12,23), or in their response to immunization with Salmonella antigens, measured either as protection from infection (32) or as delayed hypersensitivity reaction (30).…”

Section: Typhimuriummentioning

confidence: 99%

Mitogenic stimulation of murine spleen cells: relation to susceptibility to Salmonella infection

Jeney¹,

Günther²,

Jann³

1977

Infect Immun

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The screening of several inbred strains of mice suggested that the capacity of their spleen cells to respond to the mitogenic effect of lipopolysaccharide (LPS) of gram-negative bacteria was correlated with their resistance to intraperitoneal infection with Salmonella typhimurium. An injection of LPS into mice caused changes in the in vitro responsiveness of their spleen cells to the mitogenic effects of LPS and phytohemagglutinin. Pretreatment of mice with whole ultraviolet (UV)-killed bacteria led to a marked rise in the in vitro response of the spleen cells to UV-killed bacteria, but not to LPS or phytohemagglutinin. This enhanced response to UV-killed bacteria was not specific for the 0 antigens of the bacteria.

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“…Susceptibility of mice to Salmonella infections is strongly influenced by their expression of distinct versions of natural resistance-associated macrophage protein 1 (NRAMP1, also known as SLC11A1) (10), which differ by a single amino acid. When mice that are innately more resistant to virulent Salmonella are infected, thrombi can be seen in multiple sites throughout the body, including the spleen, liver, and kidneys (9,11). On the other hand, mice that, due to Nramp1, are hypersusceptible to systemic infection with virulent S. Typhimurium, such as the commonly used laboratory strains C57BL/6J and BALB/c, succumb rapidly to this infection in just a few days.…”

Section: Introductionmentioning

confidence: 99%

Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets

Hitchcock¹,

Cook²,

Bobat³

et al. 2015

Journal of Clinical Investigation

143

170

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Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver. Bacteria triggered but did not maintain this process, as thrombosis peaked at times when bacteremia was absent and bacteria in tissues were reduced by more than 90% from their peak levels. Thrombus development was triggered by an innate, TLR4-dependent inflammatory cascade that was independent of classical glycoprotein VI-mediated (GPVI-mediated) platelet activation. After infection, IFN-γ release enhanced the number of podoplanin-expressing monocytes and Kupffer cells in the hepatic parenchyma and perivascular sites and absence of TLR4, IFN-γ, or depletion of monocytic-lineage cells or CLEC-2 on platelets markedly inhibited the process. Together, our data indicate that infection-driven thrombosis follows local inflammation and upregulation of podoplanin and platelet activation. The identification of this pathway offers potential therapeutic opportunities to control the devastating consequences of infection-driven thrombosis without increasing the risk of bleeding.

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Some Physiopathological Parameters of Natural Resistance to Infection in Murine Salmonellosis

Abstract: Salmonellosis in the mouse is an infectious disease which, both as an unwanted natural event in mouse colonies and as an experimental "model" infection in the laboratory, has received considerable investigative attention.

Cited by 31 publications

References 17 publications

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

Mitogenic stimulation of murine spleen cells: relation to susceptibility to Salmonella infection

Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets

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