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J Immunol. 2015 Jul 1;195(1):194-202. doi: 10.4049/jimmunol.1401892. Epub 2015 May 29.

Deficiency of CD40 Reveals an Important Role for LIGHT in Anti-Leishmania Immunity.

Author information

1
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada;
2
Department of Immunology, Third Military Medical University, Chongqing 400038, China;
3
Department of Pathology, University of Chicago, Chicago, IL 60637;
4
Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
5
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada jude.uzonna@umanitoba.ca.

Abstract

We previously showed that LIGHT and its receptor herpes virus entry mediator (HVEM) are important for development of optimal CD4(+) Th1 cell immunity and resistance to primary Leishmania major infection in mice. In this study, we further characterized the contributions of this molecule in dendritic cell (DC) maturation, initiation, and maintenance of primary immunity and secondary anti-Leishmania immunity. Flow-cytometric studies showed that CD8α(+) DC subset was mostly affected by HVEM-Ig and lymphotoxin β receptor-Ig treatment. LIGHT signaling is required at both the priming and the maintenance stages of primary anti-Leishmania immunity but is completely dispensable during secondary immunity in wild type mice. However, LIGHT blockade led to impaired IL-12 and IFN-γ responses and loss of resistance in healed CD40-deficient mice after L. major challenge. The protective effect of LIGHT was mediated primarily via its interaction with lymphotoxin β receptor on CD8α(+) DCs. Collectively, our results show that although LIGHT is critical for maintenance of primary Th1 response, it is dispensable during secondary anti-Leishmania immunity in the presence of functional CD40 signaling as seen in wild type mice.

PMID:
26026056
DOI:
10.4049/jimmunol.1401892
[Indexed for MEDLINE]
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