Strongyloides Stercoralis and HTLV-1 Coinfection in CD34+ Cord Blood Stem Cell Humanized Mice: Alteration of Cytokine Responses and Enhancement of Larval Growth

Viral and parasitic coinfections are known to lead to both enhanced disease progression and altered disease states. HTLV-1 andStrongyloides stercoralisare co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response andS.stercoralisinfection induces a Th2 response. However, coinfection with the two pathogens has been associated with the development ofS.stercoralishyperinfection and an alteration of the Th1/Th2 balance. In this study, a model of HTLV-1 andS.stercoraliscoinfection in CD34+umbilical cord blood hematopoietic stem cell engrafted humanized mice was established. An increased level of mortality was observed in the HTLV-1 and coinfected animals when compared to theS.stercoralisinfected group. The mortality was not correlated with proviral loads or total viral RNA. Analysis of cytokine profiles showed a distinct shift towards Th1 responses in HTLV-1 infected animals, a shift towards Th2 cytokines inS.stercoralisinfected animals and elevated TNF-α responses in coinfected animals. HTLV-1 infected and coinfection groups showed a significant, yet non-clonal expansion of the CD4+CD25+T-cell population. Numbers of worms in the coinfection group did not differ from those of theS.stercoralisinfected group and no autoinfective larvae were found. However, infective larvae recovered from the coinfection group showed an enhancement in growth, as was seen in mice withS.stercoralishyperinfection caused by treatment with steroids. Humanized mice coinfected withS.stercoralisand HTLV-1 demonstrate features associated with human infection with these pathogens and provide a unique opportunity to study the interaction between these two infectionsin vivoin the context of human immune cells.