Interaction between
            <i>Yersinia pestis</i>
            and the Host Immune System

Li, Bei; Yang, Ruifu

doi:10.1128/iai.01517-07

Cited by 60 publications

(50 citation statements)

References 96 publications

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“…Studies have shown that both innate and adaptive immunity play important roles during Y. pestis infections (62). The interaction of LPS with TLR-4 represents a "double-edged sword," as overstimulation of TLR-4 results in uncontrolled production of proinflammatory cytokines, while detoxified LPS will limit TLRs' ability to stimulate innate immune responses that can subsequently affect the adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

et al. 2013

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e Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a ⌬lpp ⌬msbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ⌬msbB single mutant was minimally attenuated, the ⌬lpp single mutant and the ⌬lpp ⌬msbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the ⌬lpp ⌬msbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the ⌬lpp ⌬msbB double mutant, but not the ⌬lpp or ⌬msbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the ⌬lpp ⌬msbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the ⌬lpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the ⌬lpp ⌬msbB double mutant could provide a new live-attenuated background vaccine candidate strain, and this should be explored in the future.

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Section: Discussionmentioning

confidence: 99%

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

et al. 2013

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“…A primary underlying cause of the fulminant, extreme virulence of plague is the lack of the normal protective innate immune response to infection (7,15,20). The rapid recruitment of phagocytic cells, especially PMNs, which are able to ingest and kill invading microorganisms, is an important aspect of innate immunity.…”

Section: Discussionmentioning

confidence: 99%

Role of the Yersinia pestis Ail Protein in Preventing a Protective Polymorphonuclear Leukocyte Response during Bubonic Plague

et al. 2011

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The ability of Yersinia pestis to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. In this study, we examined the effect of Ail, a 17-kDa outer membrane protein that protects Y. pestis against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The Y. pestis ail mutant was attenuated for virulence in both rodent models. The attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but not mouse serum, to kill ail-negative Y. pestis in vitro. Intradermal infection with the ail mutant resulted in an atypical, subacute form of bubonic plague associated with extensive recruitment of polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the draining lymph node and the formation of large purulent abscesses that contained the bacteria. Systemic spread and mortality were greatly attenuated, however, and a productive adaptive immune response was generated after high-dose challenge, as evidenced by high serum antibody levels against Y. pestis F1 antigen. The Y. pestis Ail protein is an important bubonic plague virulence factor that inhibits the innate immune response, in particular the recruitment of a protective PMN response to the infected lymph node.

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“…This system secretes multiple proteins, including YopB and YopD, which insert into the plasma membrane and are thought to create a conduit called a translocon for delivery of the Yop effectors. Seven Yop effectors that are translocated into host cells have been characterized to date (22,(25)(26)(27)(28). The translocon and several of the effectors, including YopJ, YopK, and YopM, have been implicated in activating or inhibiting caspase-1 in macrophages infected with Yersinia (29-37).…”

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confidence: 99%

Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence

et al. 2016

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Being the first line of defense against invading pathogens, the innate immune system has evolved to respond to general patterns of infection, termed pathogen-associated molecular patterns (PAMPs), via pattern recognition receptors (PRRs) (1, 2). Tolllike receptors (TLRs), acting as PRRs, detect distinct PAMPs from invading bacteria, such as flagellin (TLR5) and lipopolysaccharide (LPS; TLR4). Upon PAMP recognition, TLRs activate mitogenactivated protein kinase (MAPK) and nuclear factor-B (NF-B) pathways, which direct production of host-protective factors such as proinflammatory cytokines (3, 4). Bacterial pathogens produce virulence factors that inhibit PRR-directed innate immune responses in order to promote infection (5, 6). For example, numerous Gram-negative bacterial pathogens encode type III secretion systems (T3SSs) that are used to counteract host innate immune responses (7). During bacterium-host cell contact, T3SSs are activated and translocate effectors across the plasma membrane and into the eukaryotic cytosol. Translocated effectors inhibit innate immune responses and promote pathogenesis (7,8). In order to counteract infection by virulent pathogens, host cells can sense perturbations caused by T3SSs and/or effectors and produce heightened innate immune responses (9, 10).Disruptions induced by T3SSs and/or effectors in macrophages infected with bacterial pathogens commonly result in the activation of caspase-1 (11-14). Active caspase-1 promotes maturation and secretion of cytokines such as interleukin-1␤ (IL-1␤) and IL-18, which are produced as inactive precursors. Caspase-1 is also produced as a proenzyme, and its activation typically occurs in an inflammasome, a multioligomeric complex that serves as a molecular platform for the recruitment and auto-proteolytic cleavage of procaspase-1 (11-13, 15). Active caspase-1 also induces lysosome exocytosis and a form of inflammatory cell death, termed pyroptosis, which is characterized by osmotic swelling of the macrophage and subsequent rupture of the plasma membrane, resulting in the release of proinflammatory molecules (16). Several inflammasomes have been identified, and all but one (that formed by AIM2) contain proteins that are part of the nucleotidebinding domain leucine-rich repeat (NLR) family. These NLRs serve as cytosolic PRRs and are activated upon recognition of cytosolic PAMPs or danger signals (2,11,15). For some NLRs, such as NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediates inflammasome assembly by interacting with capase-1 and the NLR (11,13,15). Complexes of NLRs and ASC form large structures in macrophages that can be detected as foci by microscopic techniques (17)(18)(19). In cases where inflammasome assembly is

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Interaction between Yersinia pestis and the Host Immune System

Cited by 60 publications

References 96 publications

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

Role of the Yersinia pestis Ail Protein in Preventing a Protective Polymorphonuclear Leukocyte Response during Bubonic Plague

Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence

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