Elevated Adaptive Immune Responses Are Associated with Latent Infections of Wuchereria bancrofti

Abstract

In order to guarantee the fulfillment of their complex lifecycle, adult filarial nematodes release millions of microfilariae (MF), which are taken up by mosquito vectors. The current strategy to eliminate lymphatic filariasis as a public health problem focuses upon interrupting this transmission through annual mass drug administration (MDA). It remains unclear however, how many rounds of MDA are required to achieve low enough levels of MF to cease transmission. Interestingly, with the development of further diagnostic tools a relatively neglected cohort of asymptomatic (non-lymphedema) amicrofilaremic (latent) individuals has become apparent. Indeed, epidemiological studies have suggested that there are equal numbers of patent (MF ⁺) and latent individuals. Since the latter represent a roadblock for transmission, we studied differences in immune responses of infected asymptomatic male individuals (n = 159) presenting either patent (n = 92 MF ⁺) or latent (n = 67 MF ⁻) manifestations of Wuchereria bancrofti. These individuals were selected on the basis of MF, circulating filarial antigen in plasma and detectable worm nests. Immunological profiles of either Th1/Th17, Th2, regulatory or innate responses were determined after stimulation of freshly isolated PBMCs with either filarial-specific extract or bystander stimuli. In addition, levels of total and filarial-specific antibodies, both IgG subclasses and IgE, were ascertained from plasma. Results from these individuals were compared with those from 22 healthy volunteers from the same endemic area. Interestingly, we observed that in contrast to MF ⁺ patients, latent infected individuals had lower numbers of worm nests and increased adaptive immune responses including antigen-specific IL-5. These data highlight the immunosuppressive status of MF ⁺ individuals, regardless of age or clinical hydrocele and reveal immunological profiles associated with latency and immune-mediated suppression of parasite transmission.

Author Summary

The tropical helminth infection lymphatic filariasis affects more than 120 million people worldwide and is considered a major public health concern. Over 90% of infections are elicited by Wucheria bancrofti and adult worms reside in the lymphatic system releasing millions of microfilariae (MF), which periodically circulate in the blood. New diagnostic tools have provided a method to determine asymptomatic patients that are amicrofilaremic: a subset of individuals that have so far been neglected but are of special interest since these patients represent a dead end in terms of parasite transmission. Therefore, we were interested in determining whether the absence of MF was associated with distinct immunological profiles and observed that indeed responses in MF ⁺ patients were dampened. From the viewpoint of the helminth such overall suppression of immune responses may facilitate MF transmission. Latent individuals however, presented elevated filarial specific responses and extrapolating these findings to the host provides novel insight into possible protective mechanisms which either actively hinders the release of MF from worms or their travel to the periphery. Further research into these aspects may broaden the range of strategies currently employed to reduce transmission and in turn eliminate bancroftian filariasis.