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. 2019 Aug 19;13(8):e0007623.
doi: 10.1371/journal.pntd.0007623. eCollection 2019 Aug.

Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells

Inge Kroidl  1   2   3 , Mkunde Chachage  1   2 , Jonathan Mnkai  2 , Anthony Nsojo  2 , Myrna Berninghoff  1 , Jaco J Verweij  4 , Lucas Maganga  2 , Nyanda E Ntinginya  2 , Leonard Maboko  2 , Petra Clowes  1   2 , Michael Hoelscher  1   2   3 , Elmar Saathoff  1   3 , Christof Geldmacher  1   3
Affiliations

Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells

Inge Kroidl et al. PLoS Negl Trop Dis. .

Abstract

Background: Susceptibility 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 findings: Two-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/significance: W. 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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Participants and their grouping according to HIV and helminth infection status.
For the analysis only HIV negative individuals with valid data for flow cytometry and W. bancrofti were included. The participants were separated into three different sub groups-.
Fig 2
Fig 2. Eosinophil counts and polyparasitism.
Eosinophil counts were available for 37 study participants without helminth infection, 87 with one helminth species, 46 with two species, and 7 with three or more helminth species. Increasing numbers of eosinophils were seen with polyparasitism. Kruskal-Wallis testing showed significant differences between groups overall (p = 0.0001) as well as Mann-Whitney testing to compare the groups separately.
Fig 3
Fig 3
A: Expression of HLADR on CD4 T cells in relation to the helminth infection status. The percentage of HLADR expressing CD4 T cells is shown for the three categories of participants. Kruskal-Wallis testing showed significant difference between groups overall (p = 0.0168). W. bancrofti-infected individuals had significantly more HLADR expressing CD4 T cells compared to helminth free individuals or study participants infected with other helminths as shown by Mann-Whitney test. B: Association of polyparasitism with activation status. Number of eosinophils is shown for participants with increasing numbers of helminth species. Kruskal-Wallis testing showed no significant difference between groups (p = 0.917) as well as Mann-Whitney test.
Fig 4
Fig 4
A: Association of helminth status with the frequency of HLA-DRpos CD38pos CD4 T cells. The percentage of HLA-DR+ CD38+ expressing CD4 T cells is shown for the three categories of participants. Kruskal-Wallis testing showed significant difference between groups overall (p = 0.044). A significant difference was seen between the subgroup of individuals without helminths and the W. bancrofti- infected participants (using Mann-Whitney testing). B: Association of polyparasitism with the frequency of HLA-DR+ CD38+ CD4 T cells. The percentage of HLA-DR+ CD38+ expressing CD4 T cells is shown for participants with increasing numbers of helminth species. Kruskal-Wallis testing showed no significant difference between groups (p = 0.262), as did the Mann-Whitney.
Fig 5
Fig 5. Correlation of effector memory cells (CD27negCD45ROpos CD4 T cells) and activation status (HLADRpos CD4 T cells).
A positive correlation was found (Spearman’s rho = 0.617, p<0.001).
See this image and copyright information in PMC

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Grants and funding

The EMINI study was funded by the European Union (SANTE/2004/078-545 and SANTE/2006/129-931). The WHIS study received funding by the German Research Foundation (DFG grant WSA 1878/1-1) with additional support by the European Community´s Seventh Framework Programme (FP7/2007-2013 and FP7/2007-2011 und EC-GA no. 241642. The testing for W. bancrofti was supported by a grant from the German Ministry of Science (BMBF, grant number 01KA0904, Surveillance of lymphatic filariasis (SOLF)).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.