BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype.
Immunologically intact BALB/c mice infected with Leishmania mexicana develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response. In order to determine the functional target(s) for IL-4/IL-13 inducing non-healing disease, the course of L. mexicana infection was monitored in mice lacking IL-4Rα expression in specific cellular compartments. A deficiency of IL-4Rα expression on macrophages/neutrophils (in LysM(cre)IL-4Rα(-/lox) animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Rα(-/flox)) mice. In contrast, CD4(+) T cell specific (Lck(cre)IL-4Rα(-/lox)) IL-4Rα(-/-) mice infected with L. mexicana developed small lesions, which subsequently healed in female mice, but persisted in adult male mice. While a strong Th1 response was manifest in both male and female CD4(+) T cell specific IL-4Rα(-/-) mice infected with L. mexicana, induction of IL-4 was manifest in males but not females, independently of CD4(+) T cell IL-4 responsiveness. Similar results were obtained using pan-T cell specific (iLck(cre)IL-4Rα(-/lox)) IL-4Rα(-/-) mice. Collectively these data demonstrate that upon infection with L. mexicana, initial lesion growth in BALB/c mice is dependent on non-T cell population(s) responsive to IL-4/IL-13 while progressive infection is dependent on CD4(+) T cells responsive to IL-4.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Karen J
KJ
Bryson
Owain R
OR
Millington
Thabang
T
Mokgethi
H Adrienne
HA
McGachy
Frank
F
Brombacher
James
J
Alexander
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007894:Leishmania mexicana / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000401:mortality*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000276:immunology*; D012737:Sex Factors; D053662:Interleukin-4 Receptor alpha Subunit
D018793:Interleukin-13; D015847:Interleukin-4; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit
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