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Pathogens 2018, 7(1), 22;

IFN-Gamma-Dependent and Independent Mechanisms of CD4+ Memory T Cell-Mediated Protection from Listeria Infection

Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
Author to whom correspondence should be addressed.
Received: 3 January 2018 / Revised: 29 January 2018 / Accepted: 11 February 2018 / Published: 13 February 2018
(This article belongs to the Special Issue Listeria monocytogenes and Its Interactions with the Host)
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While CD8+ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4+ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV), followed by a heterologous rechallenge with Listeria monocytogenes recombinantly expressing the MHC Class II-restricted LCMV epitope, GP61–80 (Lm-gp61). We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4+ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4+ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4+ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4+ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4+ memory T cells from heterologous Listeria challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role. View Full-Text
Keywords: immunological memory; secondary challenge; CD4+ T cells; Listeria monocytogenes immunological memory; secondary challenge; CD4+ T cells; Listeria monocytogenes

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Meek, S.M.; Williams, M.A. IFN-Gamma-Dependent and Independent Mechanisms of CD4+ Memory T Cell-Mediated Protection from Listeria Infection. Pathogens 2018, 7, 22.

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