Abstract
BackgroundSusceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation.Methodology/Principal findingsTwo-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DRposCD38pos CD4 T cells and effector memory cells CD4 T cells (CD45ROposCD27neg) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections.Conclusions/SignificanceW. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection.
Highlights
The human immunodeficiency virus (HIV) epidemic and high HIV transmission rates continue to affect large parts of the world [1]
The importance of CD4 T cell activation for HIV susceptibility has been emphasized in several studies focusing on HIV transmission and prevention
In this analysis we describe systemic activation of CD4 T cells in individuals infected with W. bancrofti the causative agent of lymphatic filariasis
Summary
The human immunodeficiency virus (HIV) epidemic and high HIV transmission rates continue to affect large parts of the world [1]. Different helminth infections can induce a diverse array of clinical symptoms and pathology. In addition to their associated morbidity, several distinct immunological changes have been described for different helminth species [7], some of which might potentially increase HIV susceptibility. We demonstrated for the first time an increased risk of HIV acquisition in individuals infected with the filarial nematode Wuchereria bancrofti, the agent that causes lymphatic filariasis [8]. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study.
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