Innate recognition of bacteria by a macrophage cytosolic surveillance pathway

O’Riordan, Mary X.; Yi, Caroline H.; Gonzales, Ramona; Lee, Kyung Dall; Portnoy, Daniel A.

doi:10.1073/pnas.202476699

Cited by 260 publications

(283 citation statements)

References 36 publications

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“…Another proposed mechanism of IFN-␤ induction by Gram-positive bacteria (e.g. L. monocytogenes) involves listeriolysin O-dependent liberation of bacteria and/or bacterial components from phagosomes (12,23,24). Although GAS is a prototype extracellular pathogen, it can be efficiently internalized by many phagocytic and nonphagocytic cells.…”

Section: Discussionmentioning

confidence: 99%

“…For the so far characterized induction of IFN-␤ production by Gram-positive bacteria, the expression of cytolysins was required (12,23,24). Cytolysins are thought to enable cytoplasmic escape of phagocytosed bacteria.…”

Section: Ifn-␣smentioning

confidence: 99%

“…The IFN production did not require the presence of the GAS-encoded cytolysins SLO and SLS. This finding is surprising, since during infections with other Gram-positive bacteria, either the cytolysin itself or cytolysin-mediated cytoplasmic escape of bacteria from phagocytic vesicles was implicated in triggering IFN production (12,(23)(24)(25). However, the requirement for IRF3 in the IFN production suggested that other aspects of the GAS-induced IFN production resembled the well established TBK1/IRF3 signaling pathway.…”

mentioning

confidence: 98%

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Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Gratz

Siller

Schaljo

et al. 2008

Journal of Biological Chemistry

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Bacterial pathogens are recognized by the innate immune system through pattern recognition receptors, such as Toll-like receptors (TLRs). Engagement of TLRs triggers signaling cascades that launch innate immune responses. Activation ofMAPKs and NF-B, elements of the major signaling pathways induced by TLRs, depends in most cases on the adaptor molecule MyD88. In addition, Gram-negative or intracellular bacteria elicit MyD88-independent signaling that results in production of type I interferon (IFN). Here we show that in mouse macrophages, the activation of MyD88-dependent signaling by the extracellular Gram-positive human pathogen group A streptococcus (GAS; Streptococcus pyogenes) does not require TLR2, a receptor implicated in sensing of Gram-positive bacteria, or TLR4 and TLR9. Redundant engagement of either of these TLR molecules was excluded by using TLR2/4/9 triple-deficient macrophages. We further demonstrate that infection of macrophages by GAS causes IRF3 (interferon-regulatory factor 3)-dependent, MyD88-independent production of IFN. Surprisingly, IFN is induced also by GAS lacking slo and sagA, the genes encoding cytolysins that were shown to be required for IFN production in response to other Gram-positive bacteria. Our data indicate that (i) GAS is recognized by a MyD88-dependent receptor other than any of those typically used by bacteria, and (ii) GAS as well as GAS mutants lacking cytolysin genes induce type I IFN production by similar mechanisms as bacteria requiring cytoplasmic escape and the function of cytolysins.Group A streptococcus (GAS 4 ; Streptococcus pyogenes) is an important human Gram-positive pathogen responsible for a wide spectrum of infections, ranging from mild diseases (e.g. tonsillitis) to serious illness (e.g. necrotizing fasciitis, sepsis, or severe poststreptococcal sequelae) (1). The persistence of GAS in the human population and the severity of some GAS diseases are the result of activities of a number of virulence factors that enable the pathogen to escape immune surveillance or, on contrary, induce an overreaction of the immune system (2, 3). Although GAS is generally regarded as an extracellular pathogen, recent findings suggest that GAS can survive (although not multiply) within various host cells, such as neutrophils, macrophages, epithelial cells, and fibroblasts (4 -7). The surviving bacteria may serve as a reservoir for recurrent GAS diseases.Immune responses to bacteria are initiated by recognition of bacterial components called pathogen-associated molecular patterns through host cell-encoded pattern recognition receptors (PRRs) (8, 9). Typically, pathogen-associated molecular patterns are components of the bacterial cell wall (e.g. lipopolysaccharide and lipoteichoic acid), but they may also be derived from the inside of bacteria (e.g. DNA). The primary function of PRRs is to trigger signaling cascades that activate antimicrobial defense programs. The best studied class of PRRs is the Toll-like receptor (TLR) family, which consists of 13 transmembrane glycoprote...

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Section: Discussionmentioning

confidence: 99%

Section: Ifn-␣smentioning

confidence: 99%

mentioning

confidence: 98%

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Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Gratz

Siller

Schaljo

et al. 2008

Journal of Biological Chemistry

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“…Induction of type I interferon by L. monocytogenes requires escape of intracellular bacteria into the cytosol [32,33]. In vitro experiments with cDNA microarrays have shown that L. monocytogenes infection of macrophages triggers two distinct, temporally separate waves of gene induction [33].…”

Section: Inflammatory Cytokinesmentioning

confidence: 99%

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Zenewicz

Shen

2007

Microbes and Infection

177

172

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The Gram-positive facultative intracellular bacterium Listeria monocytogenes is a model pathogen for elucidating important mechanisms of the immune response. Infection of mice with a sub-lethal dose of bacteria generates highly reproducible innate and adaptive immune responses, resulting in clearance of the bacteria and resistance to subsequent L. monocytogenes infection. Both the innate and adaptive immune systems are crucial to the recognition and elimination of this pathogen from the host.

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“…Likewise, more work will be required to determine which surveillance pathways are responsible for the detection of L. monocytogenes when these bacteria are inside the cells [55,56]. In this respect, it was recently shown that proteins belonging to the Nod protein family detect muramyl dipeptides derived from the peptidoglycan walls of Gram -bacteria [57,58].…”

Section: T Cell Primingmentioning

confidence: 99%

Mini‐review: Presentation of pathogen‐derived antigens in vivo

Lauvau

Glaichenhaus

2004

Eur J Immunol

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Most intracellular pathogens induce robust T cell responses upon infection of mammalian hosts. In most cases, these T cell responses are protective and result in pathogen clearance. It is therefore important to determine how T cells are primed and how they differentiate into cytokine-secreting and/or cytotoxic effector cells. In contrast to B cells, which recognize soluble Ag, CD8 + and CD4 + T cells react to Ag-derived peptides bound to MHC I or MHC II molecules, respectively. Therefore, elucidating the mechanisms by which pathogen-derived Ag become available for presentation is necessary to understand how pathogens trigger T cell responses in vivo. Although many excellent reviews have focused on the mechanisms involved in Ag processing, very few have pointed to the specificity of host-pathogen interactions. In this respect, it should be noticed that these interactions are very different from one pathogen to another, and may result in the involvement of different cells and molecules. Because of space limitations, we have decided to focus this review on two intracellular pathogens -vaccinia virus and Listeria monocytogenes. We have chosen these two pathogens because they both induce a strong CD8 + T cell response and because they have been extensively studied by both microbiologists and immunologists.

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Innate recognition of bacteria by a macrophage cytosolic surveillance pathway

Cited by 260 publications

References 36 publications

Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Mini‐review: Presentation of pathogen‐derived antigens in vivo

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