HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pesce, J. T. Articles by Gause, W. C. Search for Related Content PubMed PubMed Citation Articles by Pesce, J. T. Articles by Gause, W. C.

Neutrophils Clear Bacteria Associated with Parasitic Nematodes Augmenting the Development of an Effective Th2-Type Response¹

John T. Pesce^2,*, Zhugong Liu^2,, Hossein Hamed, Farhang Alem, Jeanette Whitmire, Hongxia Lin, Qian Liu, Joseph F. Urban, Jr. and William C. Gause^3,

^* Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Medicine, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ 07101; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705

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 with wild-type mice, elevations in a Gr-1^bright population in the draining lymph node was significantly decreased in CCL2^–/– mice after N. brasiliensis inoculation. Further flow cytometric and immunofluorescent analysis showed that in wild-type mice, Gr-1⁺ cells transiently entered and exited the draining lymph node shortly after N. brasiliensis inoculation. The Gr-1^bright population was comprised of neutrophils expressing TGF-β and TNF-. 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 pretreated 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI031678 and AI066188.

² J.T.P. and Z.L. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. William C. Gause, Department of Medicine, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07101. E-mail address: gausewc{at}umdnj.edu

⁴ Abbreviations used in this paper: CLN, cervical lymph node; HPRT, hypoxanthine phosphoribosyltransferase; KO, knockout; WT, wild type.