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.
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico, D.F. 14080, Mexico.
Miriam
M
Rodríguez-Sosa
Rafael
R
Saavedra
Eda P
EP
Tenorio
Lucia E
LE
Rosas
Abhay R
AR
Satoskar
Luis I
LI
Terrazas
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