| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology and Immunology and
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;
Department of Medicine, Department of Molecular Genetics and Microbiology, Department of Immunology, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, and Geriatric Research Education and Clinical Center, Veterans Affairs Medical Center, Durham, NC 27705; and
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756
TLR adaptor MyD88 activation is important in host resistance to Toxoplasma gondii during i.p. infection, but the function of this signaling pathway during oral infection, in which mucosal immunity assumes a predominant role, has not been examined. In this study, we show that MyD88–/– mice fail to control the parasite and succumb within 2 wk of oral infection. Early during infection, T cell IFN-
production, recruitment of neutrophils and induction of p47 GTPase IGTP (Irgm3) in the intestinal mucosa were dependent upon functional MyD88. Unexpectedly, these responses were MyD88-independent later during acute infection. In particular, CD4+ T cell IFN- reached normal levels independently of MyD88, despite continued absence of IL-12 in these animals. The i.p. vaccination of MyD88–/– mice with an avirulent T. gondii uracil auxotroph elicited robust IFN- responses and protective immunity to challenge with a high virulence T. gondii strain. Our results demonstrate that MyD88 is required to control Toxoplasma infection, but that the parasite can trigger adaptive immunity without the need for this TLR adaptor molecule.
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 Grants AI47888 (to E.Y.D.), AI57831 (to G.A.T.) and AI14193 (to D.J.B.) from the Public Health Service, a grant for Veterans Affairs Merit Review (to G.A.T.), and a fellowship from the King Anandamahidol Foundation (to W.S.).
2 W.S. and C.E.E. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Eric Y. Denkers, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14833. E-mail address: eyd1{at}cornell.edu
4 Abbreviations used in this paper: KO, knockout; STAg, soluble tachyzoite Ag; MLN, mesenteric lymph node; CD62L, CD62 ligand; WT, wild type; DC, dendritic cell.
This article has been cited by other articles:
|
|
 |
|
  J. P. Gigley, B. A. Fox, and D. J. Bzik Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain Infect. Immun., December 1, 2009; 77(12): 5380 - 5388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cekic, C. R. Casella, C. A. Eaves, A. Matsuzawa, H. Ichijo, and T. C. Mitchell Selective Activation of the p38 MAPK Pathway by Synthetic Monophosphoryl Lipid A J. Biol. Chem., November 13, 2009; 284(46): 31982 - 31991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Gigley, B. A. Fox, and D. J. Bzik Cell-Mediated Immunity to Toxoplasma gondii Develops Primarily by Local Th1 Host Immune Responses in the Absence of Parasite Replication J. Immunol., January 15, 2009; 182(2): 1069 - 1078. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
