A STAT4-dependent Th1 response is required for resistance to the helminth parasite Taenia crassiceps.
To determine the role of STAT4-dependent Th1 responses in the regulation of immunity to the helminth parasite Taenia crassiceps, we monitored infections with this parasite in resistant mice lacking the STAT4 gene. While T. crassiceps-infected STAT4(+/+) mice rapidly resolved the infection, STAT4(-/-) mice were highly susceptible to infection and displayed large parasite loads. Moreover, the inability of STAT4(-/-) mice to control the infection was associated with the induction of an antigen-specific Th2-type response characterized by significantly higher levels of Th2-associated immunoglobulin G1 (IgG1) and total IgE as well as interleukin-4 (IL-4), IL-10, and IL-13 than those in STAT4(+/+) mice, who produced significantly more gamma interferon. Furthermore, early after infection, macrophages from STAT4(-/-) mice produced lower levels of the pro-inflammatory cytokines IL-12, tumor necrosis factor alpha, IL-1 beta, and nitric oxide (NO) than those from STAT4(+/+) mice, suggesting a pivotal role for macrophages in mediating protection against cysticercosis. These findings demonstrate a critical role for the STAT4 signaling pathway in the development of a Th1-type immune response that is essential for mediating protection against the larval stage of T. crassiceps infection.
Rodríguez-Sosa
Miriam
M
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico, D.F. 14080, Mexico.
Saavedra
Rafael
R
Tenorio
Eda P
EP
Rosas
Lucia E
LE
Satoskar
Abhay R
AR
Terrazas
Luis I
LI
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D003551:Cysticercosis / Q000276:immunology* / Q000469:parasitology; D003552:Cysticercus / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D050797:STAT4 Transcription Factor; D013621:Taenia / Q000254:growth & development / Q000472:pathogenicity*; D018417:Th1 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D000909:Antibodies, Helminth; D016207:Cytokines; D004268:DNA-Binding Proteins; D019713:Receptors, CCR5; D017455:Receptors, IgE; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators