Document Detail


Expanded numbers of circulating myeloid dendritic cells in patent human filarial infection reflect lower CCR1 expression.
MedLine Citation:
PMID:  20956349     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
APC dysfunction has been postulated to mediate some of the parasite-specific T cell unresponsiveness seen in patent filarial infection. We have shown that live microfilariae of Brugia malayi induce caspase-dependent apoptosis in human monocyte-derived dendritic cells (DCs) in vitro. This study addresses whether apoptosis observed in vitro extends to patent filarial infections in humans and is reflected in the number of circulating myeloid DCs (mDCs; CD11c(-)CD123(lo)) in peripheral blood of infected microfilaremic individuals. Utilizing flow cytometry to identify DC subpopulations (mDCs and plasmacytoid DCs [pDCs]) based on expression of CD11c and CD123, we found a significant increase in numbers of circulating mDCs (CD11c(+)CD123(lo)) in filaria-infected individuals compared with uninfected controls from the same filaria-endemic region of Mali. Total numbers of pDCs, monocytes, and lymphocytes did not differ between the two groups. To investigate potential causes of differences in mDC numbers between the two groups, we assessed chemokine receptor expression on mDCs. Our data indicate that filaria-infected individuals had a lower percentage of circulating CCR1(+) mDCs and a higher percentage of circulating CCR5(+) mDCs and pDCs. Finally, live microfilariae of B. malayi were able to downregulate cell-surface expression of CCR1 on monocyte-derived DCs and diminish their calcium flux in response to stimulation by a CCR1 ligand. These findings suggest that microfilaria are capable of altering mDC migration through downregulation of expression of some chemokine receptors and their signaling functions. These observations have major implications for regulation of immune responses to these long-lived parasites.
Authors:
Roshanak Tolouei Semnani; Lily Mahapatra; Benoit Dembele; Siaka Konate; Simon Metenou; Housseini Dolo; Michel E Coulibaly; Lamine Soumaoro; Siaka Y Coulibaly; Dramane Sanogo; Salif Seriba Doumbia; Abdallah A Diallo; Sekou F Traoré; Amy Klion; Thomas B Nutman; Siddhartha Mahanty
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2010-10-18
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6364-72     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. rsemnani@niaid.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Brugia malayi / immunology
Cell Separation
Chemotaxis, Leukocyte / immunology
Clinical Trials as Topic
Dendritic Cells / immunology*,  metabolism
Dipetalonema Infections / immunology
Female
Filariasis / blood,  immunology*
Flow Cytometry
Humans
Male
Mansonelliasis / blood,  immunology
Middle Aged
Myeloid Cells / immunology,  metabolism
Receptors, CCR1 / biosynthesis*,  immunology
Reverse Transcriptase Polymerase Chain Reaction
Wuchereria bancrofti / immunology
Chemical
Reg. No./Substance:
0/CCR1 protein, human; 0/Receptors, CCR1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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