IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice.
Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote TH1 development. This TH1 response established resistance to Leishmania major in susceptible BALB/c mice. When present later, during the period of T cell priming, IL-4 induced TH2 differentiation and progressive leishmaniasis in resistant mice. Because immune responses developed via the consecutive activation of DCs and then T cells, the contrasting effects of IL-4 on DC development and T cell differentiation led to immune responses that had opposing functional phenotypes.
Biedermann
T
T
Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, Frauenlobstr. 9-11, 80337 Munich, Germany.
Zimmermann
S
S
Himmelrich
H
H
Gumy
A
A
Egeter
O
O
Sakrauski
A K
AK
Seegmüller
I
I
Voigt
H
H
Launois
P
P
Levine
A D
AD
Wagner
H
H
Heeg
K
K
Louis
J A
JA
Röcken
M
M
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D018320:Leishmania major / Q000276:immunology* / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C093139:LACK antigen, Leishmania; D018664:Interleukin-12; D015847:Interleukin-4; D010047:Ovalbumin