Fetal immune activation to malaria antigens enhances susceptibility to in vitro HIV infection in cord blood mononuclear cells.
Mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) remains a significant cause of new HIV infections in many countries. To examine whether fetal immune activation as a consequence of prenatal exposure to parasitic antigens increases the risk of MTCT, cord blood mononuclear cells (CBMCs) from Kenyan and North American newborns were examined for relative susceptibility to HIV infection in vitro. Kenyan CBMCs were 3-fold more likely to be infected with HIV than were North American CBMCs (P=.03). Kenyan CBMCs with recall responses to malaria antigens demonstrated enhanced susceptibility to HIV when compared with Kenyan CBMCs lacking recall responses to malaria (P=.03). CD4(+) T cells from malaria-sensitized newborns expressed higher levels of CD25 and human leukocyte antigen DR ex vivo, which is consistent with increased immune activation. CD4(+) T cells were the primary reservoir of infection at day 4 after virus exposure. Thus, prenatal exposure and in utero priming to malaria may increase the risk of MTCT.
Steiner
Kevin
K
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106-7286, USA.
Myrie
Latoya
L
Malhotra
Indu
I
Mungai
Peter
P
Muchiri
Eric
E
Dent
Arlene
A
King
Christopher L
CL
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity*; D015658:HIV Infections / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007630:Kenya; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D011247:Pregnancy
D000953:Antigens, Protozoan; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit