Infection outcome and cytokine gene expression in Brugia pahangi- infected gerbils (Meriones unguiculatus) sensitized with Brucella abortus.
Filarial infections have been associated with the development of a strongly polarized Th2 host immune response and a severe impairment of mitogen-driven proliferation and type 1 cytokine production in mice and humans. The role of this polarization in the development of the broad spectra of clinical manifestations of lymphatic filariasis is still unknown. Recently, data gathered from humans as well as from immunocompromised mouse models suggest that filariasis elicits a complex host immune response involving both Th1 and Th2 components. However, responses of a similar nature have not been reported in immunologically intact permissive models of Brugia infection. Brucella abortus-killed S19 was inoculated into the Brugia-permissive gerbil host to induce gamma interferon (IFN-gamma) production. Gerbils were then infected with B. pahangi, and the effect of the polarized Th1 responses on worm establishment and host cellular response was measured. Animals infected with both B. abortus and B. pahangi showed increased IFN-gamma and interleukin-10 (IL-10) and decreased IL-4 and IL-5 mRNA levels compared with those in animals infected with B. pahangi alone. These data suggest that the prior sensitization with B. abortus may induce a down regulation of the Th2 response associated with Brugia infection. This reduced Th2 response was associated with a reduced eosinophilia and an increased neutrophilia in the peritoneal exudate cells. The changes in cytokine and cellular environment did not inhibit the establishment of B. pahangi intraperitoneally. The data presented here suggest a complex relationship between the host immune response and parasite establishment and survival that cannot be simply ascribed to the Th1/Th2 paradigm.
Chirgwin
Sharon R
SR
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, 70803, USA.
Elzer
Philip H
PH
Coleman
Sharon U
SU
Nowling
Jena M
JM
Hagius
Sue D
SD
Edmonds
Matthew D
MD
Klei
Thomas R
TR
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002003:Brucella abortus / Q000276:immunology*; D017179:Brugia pahangi / Q000276:immunology*; D016207:Cytokines / Q000235:genetics*; D004804:Eosinophils / Q000502:physiology; D005368:Filariasis / Q000276:immunology*; D005849:Gerbillinae; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma