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Title: Neutrophils clear bacteria associated with parasitic nematodes augmenting the development of an effective Th2-type response

Author
item PESCE, JOHN - NIH BETHESDA MD
item LIU, ZHUGONG - UMDNJ NEWARK NJ
item HAMED, HOSSEIN - UMDNJ NEWARK NJ
item ALEM, FARHANG - UMDNJ NEWARK NJ
item WHITMIRE, JEANETTE - USUHU BETHESDA MD
item LIU, HONGZIA - UMDNJ NEWARK NJ
item LIU, QIAN - UMDNJ NEWARK NJ
item Urban, Joseph
item GAUSE, WILLIAM - UMDNJ NEWARK NJ

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2007
Publication Date: 1/15/2008
Citation: Pesce, J., Liu, Z., Hamed, H., Alem, F., Whitmire, J., Liu, H., Liu, Q., Urban Jr, J.F., Gause, W. 2008. Neutrophils clear bacteria associated with parasitic nematodes augmenting the development of an effective Th2-type response. Journal of Immunology. 180(1):464-474.

Interpretive Summary: Helminthic (worm) parasites can trigger highly polarized immune responses typically associated with increased numbers of CD4+ Th2 cells, eosinophils, mast cells, and basophils. There is also the potential to carry microbial pathogens into the body of the host as the parasite invades and migrates through tissues. The microbes are generally controlled by neutrophils which do not normally increase during the worm infection. If, however, there is a diminished immune response due to poor nutrition, management or mixed infections, then these secondary disease interactions become more prominent and may affect health. This study shows that blocking of neutrophil function during a worm infection that migrates through the skin can lead to an overwhelming bacterial infestation that can result in increase mortality. The bacterial infection can be controlled by application of antibiotics, but the implication is that low level infections may go undetected but can contribute to poor health since the worm serves as an important carrier of potentially harmful bacteria. This information would benefit research to optimize the health and performance of food animals since it would reduce the expression of disease.

Technical Abstract: Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node was examined after N. brasiliensis inoculation. Pronounced increases of several chemokines, including CCL2, were observed. Compared to wide type (WT) mice, a Gr-1bright population was significantly decreased in CCL2-/- mice after intracutaneous inoculation with N. brasiliensis. Further flow cytometric and immunofluorescent analysis showed that in WT mice, Gr-1+ cells transiently entered and exited the draining lymph node shortly after N. brasiliensis inoculation. The Gr-1bright population was comprised of neutrophils expressing TGF-B and TNF-a. Following Gr-1+ cell depletion, N. brasiliensis infection resulted in transient, but significantly increased levels of IFN-', increased serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality, and delayed worm expulsion. Furthermore, bacteria were readily detected in vital organs. Infection of Gr-1+ cell depleted mice with N. brasiliensis larvae that were pre-treated with antibiotics prevented bacterial dissemination, Th1 inflammatory responses, and decreases in host survival. This study indicates that parasitic nematodes can be an important vector of potentially harmful bacteria, which is typically controlled by CCL2-dependent neutrophils that ensure the optimal development of Th2 immune responses and parasite resistance.