A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3.
The immune response that is characteristic of parasitic helminth infections includes components associated with immediate-type hypersensitivity: elevated serum IgE, eosinophilia, and intestinal mast cell hyperplasia. In infection with the parasitic nematode, Heligmosomoides polygyrus, IL-4 mediates protective immunity, suggesting the presence of a host-protective Th2 response. In this investigation, we examined early stages of immune responsiveness to H. polygyrus infection to determine whether and at what stage a specific Th2-like pattern first appears. Using a quantitative reverse transcriptase-polymerase chain reaction assay, we analyzed changes in IL-2, IFN-gamma, IL-3, IL-4, IL-5, IL-6, IL-9, and IL-10 gene expression in the spleen, mesenteric lymph node, and Peyer's patch at various time points after infection. Our results demonstrate a highly specific and reproducible pattern of cytokine gene expression that remains localized to the enteric region. By 6 h after infection, IL-5 and IL-9 mRNA were elevated in the Peyer's patch and IL-3 was elevated by 12 to 24 h after infection. IL-4 RNA became elevated by 4 to 6 days after infection, but little change was observed in IFN-gamma, IL-2, or IL-10 mRNA levels. The early increases in IL-3, IL-5, and IL-9 gene expression after infection were probably T cell-independent, inasmuch as they were observed in Peyer's patches of congenitally athymic mice and anti-CD4, anti-CD8 mAb-treated conventional mice. However, treatment with these mAb considerably decreased cytokine gene expression 6 days after infection, and 8 days after infection, increased IL-4 gene expression in mesenteric lymph node cells was restricted to the CD4+ population. Thus, H. polygyrus infection induces cytokine gene expression that is restricted to some Th2-associated cytokines, is initiated by a T-independent response, and culminates in a T-dependent response.
Svetić
A
A
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Madden
K B
KB
Zhou
X D
XD
Lu
P
P
Katona
I M
IM
Finkelman
F D
FD
Urban
J F
JF
Gause
W C
WC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology; D016827:CD8 Antigens / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007114:Immunization; D007377:Interleukin-3 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000276:immunology*; D010581:Peyer's Patches / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007377:Interleukin-3