The wound repair response controls outcome to cutaneous leishmaniasis.
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.
Sakthianandeswaren
Anuratha
A
Genetics and Bioinformatics Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Elso
Colleen M
CM
Simpson
Ken
K
Curtis
Joan M
JM
Kumar
Beena
B
Speed
Terence P
TP
Handman
Emanuela
E
Foote
Simon J
SJ
D000818:Animals; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014945:Wound Healing / Q000235:genetics*