Human T-cell Leukemia Virus Type 1 and Strongyloides stercoralis: Partners in Pathogenesis

Abstract

Infection with human T-cell leukemia/lymphoma virus type 1 (HTLV-1) has been associated with various clinical syndromes including co-infection with Strongyloides stercoralis, which is an intestinal parasitic nematode and the leading cause of strongyloidiasis in humans. Interestingly, HTLV-1 endemic areas coincide with regions citing high prevalence of S. stercoralis infection, making these communities optimal for elucidating the pathogenesis of co-infection and its clinical significance. HTLV-1 co-infection with S. stercoralis has been observed for decades in a number of published patient cases and case series; however, the implications of this co-infection remain elusive. Thus far, data suggest that S. stercoralis increases proviral load in patients co-infected with HTLV-1 compared to HTLV-1 infection alone. Furthermore, co-infection with HTLV-1 has been associated with shifting the immune response from Th2 to Th1, affecting the ability of the immune system to address the helminth infection. Thus, despite this well-known association, further research is required to fully elucidate the impact of each pathogen on disease manifestations in co-infected patients. This review provides an analytical view of studies that have evaluated the variation within HTLV-1 patients in susceptibility to S. stercoralis infection, as well as the effects of strongyloidiasis on HTLV-1 pathogenesis. Further, it provides a compilation of available clinical reports on the epidemiology and pathology of HTLV-1 with parasitic co-infection as well as data from mechanistic studies suggesting possible immunopathogenic mechanisms. Furthermore, specific areas of potential future research have been highlighted to facilitate advancing understanding of the complex interactions between these two pathogens.

Keywords: ATLL; HAM/TSP; HTLV-1; co-infection; strongyloidiasis.

Figure 1

Geographical distribution of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) and Strongyloides stercoralis with overlapping areas of prevalence. Areas highly prevalent with HLTV-1 infection include Japan, Northern Australia, Africa, and South America. Areas highly prevalent with S. stercoralis infection include tropical and sub-tropical areas across the globe including sporadic infection in North America. S. stercoralis image retrieved from https://www.cdc.gov/dpdx/strongyloidiasis/index.html.

Figure 2

Mechanism for HTLV-1/S. stercoralis co-infection. HTLV-1 infected CD4+ T-cells induce a predominant Th1 response over a Th2 response and produce high production of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). This decreases the production of cytokines, IL-4 and IL-5 subsequently inhibiting B cell isotype switching to IgE and decreasing eosinophil activation, respectively and also decrease in the mast cell degranulation. The increased Th1 response also contributes to the decreased Th2 response with the release of IL-10. HTLV-1 has also been associated with an increase in Treg cells, which are CD4+CD25+FOXP3+ T-cells that lead to immunosuppression and downregulation. These cells inhibit effector T-cells and likewise help decrease the Th2 response seen in HTLV-1/S. stercoralis co-infection. With the decrease in IgE production and decreased eosinophil and mast cell activation and priming, the S. stercoralis parasite cannot be eliminated from the body. Therefore, with cases of co-infection, disseminated strongyloidiasis is likely. Moreover, the dissemination of S. stercoralis results in the IL-2/IL-2R which leads to increase in the polyclonal expansion of HTLV-1 infected T-cells which leads to these sequences of events.