The wound repair response controls outcome to cutaneous leishmaniasis
- Anuratha Sakthianandeswaren†,‡,
- Colleen M. Elso†,
- Ken Simpson†,
- Joan M. Curtis§,
- Beena Kumar§,
- Terence P. Speed†,
- Emanuela Handman§,¶, and
- Simon J. Foote†,¶,∥,††
- †Genetics and Bioinformatics Division and §Department of Infection and Immunity, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050, Australia; ‡Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia; and ∥Menzies Research Institute, 17 Liverpool Street, Hobart, Tasmania 7000, Australia
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Edited by Louis H. Miller, National Institutes of Health, Bethesda, MD, and approved August 5, 2005 (received for review July 5, 2005)
Abstract
Chronic microbial infections are associated with fibrotic and inflammatory reactions known as granulomas showing similarities to wound-healing and tissue repair processes. We have previously mapped three leishmaniasis susceptibility loci, designated lmr1, -2, and -3, which exert their effect independently of T cell immune responses. Here, we show that the wound repair response is critically important for the rapid cure in murine cutaneous leishmaniasis caused by Leishmania major. Mice congenic for leishmaniasis resistance loci, which cured their lesions more rapidly than their susceptible parents, also expressed differentially genes involved in tissue repair, laid down more ordered collagen fibers, and healed punch biopsy wounds more rapidly. Fibroblast monolayers from these mice repaired in vitro wounds faster, and this process was accelerated by supernatants from infected macrophages. Because these effects are independent of T cell-mediated immunity, we conclude that the rate of wound healing is likely to be an important component of innate immunity involved in resistance to cutaneous leishmaniasis.
Footnotes
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↵ †† To whom correspondence should be addressed. E-mail: foote{at}wehi.edu.au.
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↵ ¶ E.H. and S.J.F. contributed equally to this work.
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Author contributions: A.S., C.M.E., E.H., and S.J.F. designed research; A.S., C.M.E., J.M.C., and B.K. performed research; A.S., C.M.E., K.S., T.P.S., E.H., and S.J.F. analyzed data; and E.H. and S.J.F. wrote the paper.
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This paper was submitted directly (Track II) to the PNAS office.
- Copyright © 2005, The National Academy of Sciences
