Expanded numbers of circulating myeloid dendritic cells in patent human filarial infection reflect lower CCR1 expression.
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.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. rsemnani@niaid.nih.gov
Roshanak Tolouei
RT
Semnani
Lily
L
Mahapatra
Benoit
B
Dembele
Siaka
S
Konate
Simon
S
Metenou
Housseini
H
Dolo
Michel E
ME
Coulibaly
Lamine
L
Soumaoro
Siaka Y
SY
Coulibaly
Dramane
D
Sanogo
Salif
S
Seriba Doumbia
Abdallah A
AA
Diallo
Sekou F
SF
Traoré
Amy
A
Klion
Thomas B
TB
Nutman
Siddhartha
S
Mahanty
D000328:Adult; D000818:Animals; D017178:Brugia malayi / Q000276:immunology; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004154:Dipetalonema Infections / Q000276:immunology; D005260:Female; D005368:Filariasis / Q000097:blood / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008366:Mansonella; D008368:Mansonelliasis / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D054389:Receptors, CCR1 / Q000096:biosynthesis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014958:Wuchereria bancrofti / Q000276:immunology
C515300:CCR1 protein, human; D054389:Receptors, CCR1