Adaptive Immunity against<i>Listeria monocytogenes</i>in the Absence of Type I Tumor Necrosis Factor Receptor p55

White, Douglas W.; Badovinac, Vladimir P.; Fan, Xueli; Harty, John T.

doi:10.1128/iai.68.8.4470-4476.2000

Cited by 24 publications

(20 citation statements)

References 40 publications

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“…This is in line with previous reports showing a critical role of cell-mediated immunity of CD8 T cells in controlling infection. 31,32 To assess whether membraneexpressed TNF on lymphocytes could confer protection, lymphocytes from immunized mice were transferred into TNF Ϫ/Ϫ mice. Splenocytes from mem-TNF mice, but not TNF Ϫ/Ϫ mice, conferred protection.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, TNF appears not to be required for an antigen-specific immune response, consistent with previous reports. 31,32 We next asked whether membrane TNF expressed on antigen-specific lymphocytes was sufficient to confer effective protection in vivo. To this end, TNF Ϫ/Ϫ mice received splenic lymphocytes (2 ϫ 10 7 cells, 95% lymphocytes) from wild-type, mem-TNF mice, or TNF Ϫ/Ϫ mice, either naïve or preinfected for 7 days with ActA-deficient LM strain (10 6 CFU).…”

Section: T-cell Response To Lm and Protection Of Tnfdeficient Mice Bymentioning

confidence: 99%

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Membrane Tumor Necrosis Factor Confers Partial Protection to Listeria Infection

Torres

Janot

Quesniaux

et al. 2005

The American Journal of Pathology

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Tumor necrosis factor (TNF) plays a critical role in the host response to the intracellular pathogen Listeria monocytogenes (LM). TNF exists in soluble and membrane-bound forms and exhibits both unique and overlapping activities. We examined the role of membrane TNF in the absence of secreted TNF for host resistance in knockin mice in which the endogenous TNF was replaced by a regulated, noncleavable allele (mem-TNF). Macrophages expressing mem-TNF produced nitric oxide and displayed normal bactericidal activity. Although mice completely deficient in TNF (TNF ؊/؊ ) succumbed to LM infection within 4 days, mem-TNF mice controlled LM infection at a low dose (10 4 CFU) but succumbed at a higher dose of infection (10 5 CFU). In contrast to complete TNF deficiency, mem-TNF mice developed confined microabscesses that expressed inducible nitric oxide synthase. The transfer of lymphocytes from immunized mem-TNF, but not TNF ؊/؊ , mice protected TNF ؊/؊ mice from fatal infection. Taken Protective immunity to Listeria monocytogenes (LM) infection, both in humans and experimental animals, is based on orchestrated action of T cells, macrophages, and cytokines, including interferon (IFN)-␥, interleukin (IL)-12, and tumor necrosis factor (TNF). 1 A critical role for TNF in anti-LM defense is inferred from neutralization and gene deletion experiments in mice. 2,3 In addition, the TNFrelated cytokines lymphotoxin (LT)-␣ and LT-␤ are also required to control LM infection. 4 Both secreted TNF and LT-␣ signal through p55 and p75 TNF receptors (TNFR1 and TNFR2, respectively). The cell-bound LT-␣␤ heterotrimers recognize the LT-␤R. TNF-R1 signaling appears to be critical for the control of LM infection 2,3 and LT-␤R also plays a distinct role, while the contribution of TNFR2 is less well defined.TNF is expressed by a variety of cells, including macrophages and T cells, and is a major regulator of inflammation and leukocyte trafficking. 5 TNF is first produced as an integral membrane protein and is subsequently cleaved by the metalloproteinase-disintegrin TACE (TNF-␣ converting enzyme) 6,7 into the secreted trimeric TNF. Although the role of TNF in controlling intracellular bacterial infections is uncontested, the function of membrane TNF in host resistance is less understood.Several biological functions of membrane TNF have been described, such as cytotoxicity, polyclonal activation of B cells, induction of IL-10 by monocytes, induction of chemokines, and ICAM-1 expression on endothelial cells. 8 -10 The transgenic overexpression of membrane TNF has demonstrated an in vivo role in the control of LM and mycobacterial infection. [11][12][13] However, these models were potentially nonphysiological as transgenic expression of a membrane-only form of TNF results in artificially high and nonselective expression of membrane TNF. The recent generation of mice with functional, normally regulated and expressed membrane-bound TNF, obtained by knocking-in an uncleavable ⌬1-9, K11E TNF allele (mem-TNF mice), represents a major advance and allo...

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Section: Discussionmentioning

confidence: 99%

Section: T-cell Response To Lm and Protection Of Tnfdeficient Mice Bymentioning

confidence: 99%

Membrane Tumor Necrosis Factor Confers Partial Protection to Listeria Infection

Torres

Janot

Quesniaux

et al. 2005

The American Journal of Pathology

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“…Surprisingly, neither IFN-+ , TNF- § nor IL-12 is required for the development of a protective CD8 + T cell response [47,[52][53][54]. However, studies in which mice were injected with live bacteria or HKLM strongly supported the idea that innate mechanisms had a strong impact on the quality of the T cell response [36].…”

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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“…Within an infected cell, unipolar expression of ActA by Lm facilitates and is required for bacterium to recruit host cell actin into organized tails, allowing for intracellular spread leading to a productive infection (25). We and others have demonstrated that infection with the ⌬actA Lm mutant is able to prime Lm-specific CD8 and CD4 T cells, and yet is nonlethal even at relatively high inocula (up to 10 6 CFUs) in mice deficient in components of innate immunity such as MyD88, IFN-␥, or TNF-␣ receptor normally essential for protection from WT Lm infection (20,26,27). To verify that the absence of either IL-12 or IFN-IR signaling does not significantly alter the Lm load following infection with Lm-OVA ⌬actA, we examined the number of bacteria in the spleen of IFN-IR Ϫ/Ϫ , IL-12P40 Ϫ/Ϫ , and control mice following infection with 10 6 CFUs of Lm-OVA ⌬actA (Fig.…”

Section: Relative Roles Of Il-12 and Ifn-i Signaling In The Host For mentioning

confidence: 99%

IL-12 and Type-I IFN Synergize for IFN-γ Production by CD4 T Cells, Whereas Neither Are Required for IFN-γ Production by CD8 T Cells afterListeria monocytogenesInfection

Way

Havenar-Daughton

Kolumam

et al. 2007

The Journal of Immunology

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Differentiation of Ag-specific T cells into IFN-γ producers is essential for protective immunity to intracellular pathogens. In addition to stimulation through the TCR and costimulatory molecules, IFN-γ production is thought to require other inflammatory cytokines. Two such inflammatory cytokines are IL-12 and type I IFN (IFN-I); both can play a role in priming naive T cells to produce IFN-γ in vitro. However, their role in priming Ag-specific T cells for IFN-γ production during experimental infection in vivo is less clear. In this study, we examine the requirements for IL-12 and IFN-I, either individually or in combination, for priming Ag-specific T cell IFN-γ production after Listeria monocytogenes (Lm) infection. Surprisingly, neither individual nor combined defects in IL-12 or IFN-I signaling altered IFN-γ production by Ag-specific CD8 T cells after Lm infection. In contrast, individual defects in either IL-12 or IFN-I signaling conferred partial (∼50%) reductions, whereas combined deficiency in both IL-12 and IFN-I signaling conferred more dramatic (75–95%) reductions in IFN-γ production by Ag-specific CD4 T cells. The additive effects of IL-12 and IFN-I signaling on IFN-γ production by CD4 T cells were further demonstrated by adoptive transfer of transgenic IFN-IR+/+ and IFN-IR−/− CD4 T cells into normal and IL-12-deficient mice, and infection with rLm. These results demonstrate an important dichotomy between the signals required for priming IFN-γ production by CD4 and CD8 T cells in response to bacterial infection.

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Adaptive Immunity againstListeria monocytogenesin the Absence of Type I Tumor Necrosis Factor Receptor p55

Cited by 24 publications

References 40 publications

Membrane Tumor Necrosis Factor Confers Partial Protection to Listeria Infection

Membrane Tumor Necrosis Factor Confers Partial Protection to Listeria Infection

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

IL-12 and Type-I IFN Synergize for IFN-γ Production by CD4 T Cells, Whereas Neither Are Required for IFN-γ Production by CD8 T Cells afterListeria monocytogenesInfection

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