This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Mishra, B. B.
Right arrow Articles by Teale, J. M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mishra, B. B.
Right arrow Articles by Teale, J. M.

 Previous Article  |  Next Article 

Infection and Immunity, December 2009, p. 5369-5379, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00455-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

MyD88-Deficient Mice Exhibit Decreased Parasite-Induced Immune Responses but Reduced Disease Severity in a Murine Model of Neurocysticercosis{triangledown}

Bibhuti B. Mishra,1,{dagger} Uma Mahesh Gundra,1,{dagger} Kondi Wong,2 and Judy M. Teale1*

Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-1644,1 Department of Pathology, Tampa General Hospital, One Tampa Circle, Tampa, Florida 336062

Received 22 April 2009/ Returned for modification 29 May 2009/ Accepted 18 September 2009

The symptomatic phase of neurocysticercosis (NCC), a parasitic disease of the central nervous system (CNS) in humans, is characterized by inflammatory responses leading to neuropathology and, in some cases, death. In an animal model of NCC in which mice were intracranially inoculated with the parasite Mesocestoides corti, the infection in mice lacking the myeloid differentiation primary response gene 88 (MyD88–/–) resulted in decreased disease severity and improved survival compared with that in wild-type (WT) mice. The CNS of MyD88–/– mice was more quiescent, with decreased microgliosis and tissue damage. These mice exhibited substantially reduced primary and secondary microglial nodule formations and lacked severe astrogliotic reactions, which were seen in WT mice. Significantly reduced numbers of CD11b+ myeloid cells, {alpha}β T cells, {gamma}{delta} T cells, and B cells were present in the brains of MyD88–/– mice in comparison with those of WT mice. This decrease in cellular infiltration correlated with a decrease in blood-brain barrier permeability, as measured by reduced fibrinogen extravasation. Comparisons of cytokine expression indicated a significant decrease in the CNS levels of several inflammatory mediators, such as tumor necrosis factor alpha, gamma interferon, CCL2, and interleukin-6, during the course of infection in MyD88–/– mice. Collectively, these findings suggest that MyD88 plays a prominent role in the development of the hyperinflammatory response, which in turn contributes to neuropathology and disease severity in NCC.

* Corresponding author. Mailing address: Department of Biology, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-1644. Phone: (210) 458-7024. Fax: (210) 458-7025. E-mail: judy.teale{at}utsa.edu

{triangledown} Published ahead of print on 28 September 2009.

Editor: J. F. Urban, Jr.

{dagger} B.B.M. and U.M.G. contributed equally to this work.

Infection and Immunity, December 2009, p. 5369-5379, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00455-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»