Impairment of alternative macrophage activation delays cutaneous leishmaniasis in nonhealing BALB/c mice.
Expressed on various cell types, the IL-4Ralpha is a component of both receptors for IL-4 and IL-13. Susceptibility of BALB/c mice to Leishmania major is believed to be dependent on the development of IL-4- and IL-13-producing Th2 cells, while IFN-gamma secretion by Th1 cells is related to resistance. Despite a sustained development of Th2 cells, IL-4Ralpha-deficient BALB/c mice are able to control acute cutaneous leishmaniasis, suggesting that IL-4Ralpha-bearing cells other than Th2 cells contribute to susceptibility. To analyze the contribution of the IL-4Ralpha on macrophages, recently generated macrophage/neutrophil-specific IL-4Ralpha-deficient mice on a susceptible BALB/c genetic background were infected with L. major. Strikingly, macrophage/neutrophil-specific IL-4Ralpha-deficient mice showed a significantly delayed disease progression with normal Th2 and type 2 Ab responses but improved macrophage leishmanicidal effector functions and reduced arginase activity. Together, these results suggest that alternative macrophage activation contributes to susceptibility in cutaneous leishmaniasis.
Hölscher
Christoph
C
Institute for Infectious Diseases and Molecular Medicine and Division of Immunology, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
Arendse
Berenice
B
Schwegmann
Anita
A
Myburgh
Elmarie
E
Brombacher
Frank
F
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit
D000913:Antibodies, Protozoan; D007371:Interferon-gamma; D015847:Interleukin-4; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit