CD16 Expression on Monocytes in Healthy Individuals but Not Schistosome-Infected Patients Is Positively Associated with Levels of Parasite-Specific IgG and IgG1

Abstract

Human IgG1 antibody responses are associated with protection against Schistosoma haematobium infection and are now a target for schistosome vaccine development. This study aimed to investigate the relationship between total IgG and the IgG subclasses and the monocyte IgG receptor, known as FcγRIIIa or CD16, in schistosome exposed people. Systemic levels of schistosome-specific anti-adult worm total IgG and IgG subclass titres were measured by ELISA in 100 individuals from an S. haematobium endemic area in Zimbabwe and, using parametric statistical methods and regression analysis, related to the levels of CD16 expression on individuals' circulating monocytes, determined via flow cytometry. Monocyte CD16 expression rose with parasite-specific total IgG and IgG1 in healthy participants, but not in schistosome infected patients. Similar to parasite-specific IgG and IgG1, CD16 expression in healthy individuals is associated with protection against schistosome infection. This relationship indicates a mechanistic link between the innate and adaptive immune responses to helminth infection in protection against infection. Further understanding the elements of a protective immune response in schistosomiasis may aid in efforts to develop a protective vaccine against this disease.

Author Summary

Schistosomiasis is a parasitic disease caused by the parasite Schistosoma spp. Over 240 million people are infected worldwide, mainly in Sub-Saharan Africa, but an efficacious, protective vaccine has yet to be found. Protection against schistosome infection in individuals living in endemic areas is mediated by antibodies. In particular, IgG1 antibody has been shown to be protective against infection in individuals living in endemic areas, and eliciting IgG1 production has become a cornerstone of vaccine development efforts. However, little is known about the mechanisms by which IgG1 induces protection. The cell surface molecule CD16 is an IgG antibody receptor expressed on monocytes and binds preferentially to IgG antibody subclasses. The work presented here thus investigates the relationship between IgG levels and the monocyte CD16 receptor in a population endemically exposed to infection with schistosomes. We present results linking CD16 expression with IgG1 levels, whereby uninfected individuals have a positive relationship between IgG1 and CD16 expression levels, while schistosome infected individuals did not show any statistically significant relationship between the two. Thus we provide evidence to suggest a mechanistic link between the innate and adaptive immune response in parasitic infection, associating monocyte CD16 expression with a protective immune response.