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.
Semnani
Roshanak Tolouei
RT
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. rsemnani@niaid.nih.gov
Mahapatra
Lily
L
Dembele
Benoit
B
Konate
Siaka
S
Metenou
Simon
S
Dolo
Housseini
H
Coulibaly
Michel E
ME
Soumaoro
Lamine
L
Coulibaly
Siaka Y
SY
Sanogo
Dramane
D
Seriba Doumbia
Salif
S
Diallo
Abdallah A
AA
Traoré
Sekou F
SF
Klion
Amy
A
Nutman
Thomas B
TB
Mahanty
Siddhartha
S
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