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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Weng, M. Articles by Shi, H. N. Search for Related Content PubMed PubMed Citation Articles by Weng, M. Articles by Shi, H. N.

Alternatively Activated Macrophages in Intestinal Helminth Infection: Effects on Concurrent Bacterial Colitis¹

Mucosal Immunology Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129

The distribution of several pathogenic helminth infections coincides geographically with many devastating microbial diseases, including enteric bacterial infections. To dissect the mechanisms by which helminths modulate the host’s response to enteric bacteria and bacteria-mediated intestinal inflammation, we have recently established a coinfection model and shown that coinfection with the helminth Heligmosomoides polygyrus exacerbates colitis induced by infection with the Gram-negative bacterial pathogen Citrobacter rodentium. The disease severity of the coinfected mice was correlated with high Citrobacter loads in the gut, translocation of the bacteria into mucosal and systemic immune compartments, delayed bacterial clearance, and a significantly enhanced colonic TNF- response. In the present study, using our in vivo coinfection model as well as in vitro approaches, we test the hypothesis that the phenotypic and functional alterations in macrophages induced by the helminth-driven T cell response may contribute to the observed alterations in the response to C. rodentium. We show that via a STAT6-dependent mechanism H. polygyrus coinfection results in a marked infiltration into the colonic lamina propria of F4/80⁺ cells that have the phenotype of alternatively activated macrophages. Functional analysis of these macrophages further shows that they are impaired in their killing of internalized bacteria. Yet, these cells produce an enhanced amount of TNF- in response to C. rodentium infection. These results demonstrate that helminth infection can impair host protection against concurrent enteric bacterial infection and promote bacteria-induced intestinal injury through a mechanism that involves the induction of alternatively activated macrophages.

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 in part by the Clinical Nutrition Research Center at Harvard (P30 DK 40561) and a RO1 grant (to B.J.C.). H.N.S. is a recipient of National Institutes of Health KO1 Award (DK059996). M.W. is sponsored by Fogarty International Maternal and Child Health Research and Training Program (TW001265). O.F.-J. is sponsored by the Harvard Medical School Training Program in Nutrition and Metabolism (5 T32 HD052961).

² Address correspondence and reprint requests to Dr. Hai Ning Shi, Mucosal Immunology Laboratory, Massachusetts General Hospital, Building 114 16th Street, Room 3504, Charlestown, Massachusetts, 02129. E-mail address: shiha{at}helix.mgh.harvard.edu

³ Abbreviations used in this paper: LP, lamina propria; Arg1, arginase 1; DC, dendritic cell; iNOS, inducible NO synthase; KO, knockout; LB, Luria broth; MLN, mesenteric lymph node.

This article has been cited by other articles:

				H.-W. Koon, Y. S. Kim, H. Xu, A. Kumar, D. Zhao, I. Karagiannides, P. R. Dobner, and C. Pothoulakis Neurotensin induces IL-6 secretion in mouse preadipocytes and adipose tissues during 2,4,6,-trinitrobenzensulphonic acid-induced colitis PNAS, May 26, 2009; 106(21): 8766 - 8771. [Abstract] [Full Text] [PDF]

				L. E. Bazzone, P. M. Smith, L. I. Rutitzky, M. G. Shainheit, J. F. Urban, T. Setiawan, A. M. Blum, J. V. Weinstock, and M. J. Stadecker Coinfection with the Intestinal Nematode Heligmosomoides polygyrus Markedly Reduces Hepatic Egg-Induced Immunopathology and Proinflammatory Cytokines in Mouse Models of Severe Schistosomiasis Infect. Immun., November 1, 2008; 76(11): 5164 - 5172. [Abstract] [Full Text] [PDF]