Immunity to intracellular bacteria

Kaufmann, Stefan H. E.; Follows, George; Munik, Martin E.

doi:10.1590/s0074-02761992000900013

Cited by 121 publications

(181 citation statements)

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“…In vivo, the response against intracellular bacteria is associated with the formation of granulomas (36). IFN-␥ promotes the formation of granulomas in Mycobacterium bovis infection, leading to the control of bacterial growth (37).…”

Section: Discussionmentioning

confidence: 99%

IFN-γ-Induced Apoptosis and Microbicidal Activity in Monocytes Harboring the Intracellular Bacterium Coxiella burnetii Require Membrane TNF and Homotypic Cell Adherence

Dellacasagrande

Ghigo

Raoult

et al. 2002

The Journal of Immunology

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IFN-gamma is critical for the protection against intracellular bacteria through activation of the antimicrobial machinery of phagocytes. Coxiella burnetii, the etiological agent of Q fever, is a strictly intracellular bacterium that inhabits monocytes/macrophages. We previously showed that IFN-gamma induced C. burnetii killing by promoting the apoptosis of infected monocytes. We show in this study that IFN-gamma-induced apoptosis of infected monocytes was characterized by a time- and dose-dependent activation of caspase-3. IFN-gamma-mediated caspase-3 activation and C. burnetii killing depend on the expression of membrane TNF. Indeed, TNF was transiently expressed on the cell surface of infected monocytes a few hours after IFN-gamma treatment. In addition, anti-TNF Abs inhibited IFN-gamma-mediated caspase-3 activation whereas soluble TNF had no effect on infected cells. Concomitantly, IFN-gamma induced homotypic adherence of C. burnetii-infected monocytes. The latter required the interaction of beta(2) integrins with CD54. When adherence was disrupted by pipetting, by a combination of Abs specific for CD11b, CD18, and CD54, or by an antisense oligonucleotide targeting CD18 mRNA, both cell apoptosis and bacterial killing induced by IFN-gamma were inhibited. Thus, adherence via CD54/beta(2) integrins together with membrane TNF are required to eliminate C. burnetii-infected cells through cell contact-dependent apoptosis. Our results reveal a new component of the antimicrobial arsenal mobilized by IFN-gamma against infection by intracellular bacteria.

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Section: Discussionmentioning

confidence: 99%

IFN-γ-Induced Apoptosis and Microbicidal Activity in Monocytes Harboring the Intracellular Bacterium Coxiella burnetii Require Membrane TNF and Homotypic Cell Adherence

Dellacasagrande

Ghigo

Raoult

et al. 2002

The Journal of Immunology

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“…Development of Th1 cells is regulated by the Th1-specific transcription factor T-bet (Szabo et al, 2000) while the transcription factors retinoid-related orphan receptor gamma-t (RORγt) and RORα specify the Th17 lineage (Ivanov et al, 2006; Yang et al, 2008). Th1 cells produce interferon-γ (IFN-γ) and are best equipped to clear intracellular bacteria and viruses, while Th17 cells produce interleukin (IL-17A), IL-17F, IL-21 and IL-22 to protect mucosal surfaces against extracellular bacteria and fungi (Kaufmann, 1993; Khader et al, 2009). However, deregulated Th responses can increase susceptibility to autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

The Transcription Factors T-bet and Runx Are Required for the Ontogeny of Pathogenic Interferon-γ-Producing T Helper 17 Cells

et al. 2014

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SUMMARY T helper 17 (Th17) cells can give rise to interleukin-17A (IL-17A) and interferon (IFN)-γ-double producing cells that are implicated in development of autoimmune diseases. However, the molecular mechanisms that govern generation of IFN-γ-producing Th17 cells are unclear. We found that co-expression of the Th1- and Th17-cell master transcription factors, T-bet and retinoid-related orphan receptor gamma-t (RORγt), respectively, did not generate Th cells with robust IL-17 and IFN-γ expression. Instead, development of IFN-γ-producing Th17 cells required T-bet and Runx1 or Runx3. IL-12-stimulated Th17 cells upregulated Runx1, which bound to the Ifng locus in a T-bet dependent manner. Reciprocally, T-bet or Runx1 deficiency, or inhibition of Runx transcriptional activity, impaired the development of IFN-γ-producing Th17 cells, during experimental autoimmune encephalomyelitis, which correlated with substantially ameliorated disease course. Thus, our studies identify a critical role for T-bet and Runx transcription factors in the generation of pathogenic IFN-γ-producing Th17 cells.

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“…Although L. monocytogenes is not commonly associated with secondary bacterial infections during influenza infection, it was used here because it provides an excellent model of a systemic bacterial infection. The innate immune system is triggered rapidly after infection with L. monocytogenes , and it is crucial for early control of bacterial replication (Kaufmann, 1993). Two cytokines are important components of the innate immune response to L. monocytogenes , IL-6 and IFN-γ (Andersson et al, 1998; Dai et al, 1997; Dalrymple et al, 1995; Kopf et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Influenza Virus-Induced Glucocorticoids Compromise Innate Host Defense against a Secondary Bacterial Infection

Jamieson

Annicelli

et al. 2010

Cell Host & Microbe

146

121

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Summary Multicellular organisms are continuously exposed to many different pathogens. Because different classes of pathogens require different types of immune responses, understanding how an ongoing immune response to one type of infection affects the host’s ability to respond to another pathogen is essential for a complete understanding of host-pathogen interactions. Here we used a mouse model of co-infection to gain insight into the effect of respiratory influenza virus infection on a subsequent systemic bacterial infection. We found that influenza infection triggered a generalized stress response leading to a sustained increase in serum glucocorticoid levels, resulting in a systemic suppression of immune responses. However, virus-induced glucocorticoid production was necessary to control the inflammatory response and prevent lethal immunopathology during co-infection. This study demonstrates that activation of the hypothalamic-pituitary-adrenal axis controls the balance between immune defence and immunopathology, and is an important component of the host response to co-infection.

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Immunity to intracellular bacteria

Cited by 121 publications

References 0 publications

IFN-γ-Induced Apoptosis and Microbicidal Activity in Monocytes Harboring the Intracellular Bacterium Coxiella burnetii Require Membrane TNF and Homotypic Cell Adherence

IFN-γ-Induced Apoptosis and Microbicidal Activity in Monocytes Harboring the Intracellular Bacterium Coxiella burnetii Require Membrane TNF and Homotypic Cell Adherence

The Transcription Factors T-bet and Runx Are Required for the Ontogeny of Pathogenic Interferon-γ-Producing T Helper 17 Cells

Influenza Virus-Induced Glucocorticoids Compromise Innate Host Defense against a Secondary Bacterial Infection

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