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Lymphotoxin alpha beta 2 (Membrane lymphotoxin) is critically important for resistance to Leishmania major infection in mice
journal contributionposted on 2023-05-17, 07:47 authored by Xu, G, Liu, D, Fan, Y, Yang, X, Heinrich KornerHeinrich Korner, Fu, YX, Uzonna, JE
Although the essential role of TNF-Î± in the control of intracellular pathogens including Leishmania major is well established, it is uncertain whether the related cytokine lymphotoxin Î±Î²2 (LTÎ±1Î²2, membrane lymphotoxin) plays any role in this process. In this study, we investigated the contribution of membrane lymphotoxin in host response to L. major infection by using LTÎ²-deficient (LTÎ²-/-) mice on the resistant C57BL/6 background. Despite mounting early immune responses comparable to those of wild-type (WT) mice, LTÎ²-/- mice developed chronic nonhealing cutaneous lesions due to progressive and unresolving inflammation that is accompanied by uncontrolled parasite proliferation. This chronic disease was associated with striking reduction in IL-12 and Ag-specific IFN-Î³ production by splenocytes from infected mice. Consistent with defective cellular immune response, infected LTÎ²-/- mice had significantly low Ag-specific serum IgG1 and IgG2a levels compared with WT mice. Although administration of rIL-12 to L. major-infected LTÎ²-/- mice caused complete resolution of chronic lesions, it only partially (but significantly) reduced parasite proliferation. In contrast, blockade of LIGHT signaling in infected LTÎ²-/- mice resulted in acute and progressive lesion development, massive parasite proliferation, and dissemination to the visceral organs. Although infected LTÎ²-/- WT bone marrow chimeric mice were more resistant than LTÎ²-/- mice, they still had reduced ability to control parasites and showed defective IL-12 and IFN-Î³ production compared with infected WT mice. These results suggest that membrane lymphotoxin plays critical role in resistance to L. major by promoting effective T cell-mediated anti-Leishmania immunity. Copyright Â© 2007 by The American Association of Immunologists, Inc.
Publication titleJournal of Immunology
Department/SchoolMenzies Institute for Medical Research
PublisherAmer Assoc Immunologists
Place of publication9650 Rockville Pike, Bethesda, USA, Md, 20814