The TGF-beta response to Leishmania chagasi in the absence of IL-12.
Cure of leishmaniasis requires a type 1 immune response characterized by IFN-gamma production. Leishmania major infection leads to a type 2 response suppressing cure of susceptible BALB/c mice, and L. major causes an exacerbated type 2 response in mouse strains with a gene knockout (KO) such that they lack IL-12p40 (IL-12KO mice). In contrast, type 1 responses are inhibited by TGF-beta without Th2 cell expansion in BALB/c mice infected with L. chagasi. We questioned whether the type 2 or the TGF-beta response would dominate during L. chagasi infection of IL-12KO mice. C57BL/6 mice developed self-resolving L. chagasi infection with abundant IFN-gamma. In contrast, L. chagasi disease was exacerbated and IFN-gamma was low in IL-12KO mice. Total TGF-beta was significantly higher in IL-12KO than control C57BL/6 mice, but IL-4 and IL-10 levels were similar. TGF-beta was further augmented in IL-12/IFN-gamma double-KO mice. Thus, in contrast to L. major, the TGF-beta response was exacerbated whereas type 2 cells were not expanded during L. chagasi infection of IL-12KO mice. We conclude that L. chagasi has an inherent propensity to elicit a prominent TGF-beta response that either suppresses, or is suppressed by, a type 1 response. We propose this be termed a "type 3" immune response, which can antagonize a type 1 response.
Wilson
Mary E
ME
Veterans' Affairs Medical Center, Department of Internal Medicine, University of Iowa, Iowa City 52242, USA. mary-wilson@uiowa.edu
Recker
Thomas J
TJ
Rodriguez
Nilda E
NE
Young
Betty M
BM
Burnell
Kindra K
KK
Streit
Judy A
JA
Kline
Joel N
JN
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma