Correlation between Eosinophils and Protection against Reinfection withSchistosoma mansoniand the Effect of Human Immunodeficiency Virus Type 1 Coinfection in Humans

Abstract

Longitudinal investigations of an adult male population of Kenyan car washers who have heavy and quantifiable occupational exposure to Schistosoma mansoni cercariae revealed that some individuals develop resistance to reinfection while others remain highly susceptible. We sought to characterize immune correlates associated with host protection in this population. Previous studies have demonstrated an association of peripheral eosinophilia with resistance to reinfection with schistosomes. Thus, we investigated the relationship between the percentage of circulating eosinophils and the effect of human immunodeficiency virus type 1 (HIV-1) coinfection on the susceptibility of the car washers to reinfection with schistosomes. Elevated percentages of circulating eosinophils were associated with resistance to reinfection by S. mansoni in HIV-1-seronegative persons. In the HIV-1-seropositive cohort, low CD4؉ -T-cell counts were associated with a less intense eosinophilia. Moreover, eosinophils from the car washers expressed high levels of Fc⑀RI ␤ chain, a molecule important in immunoglobulin E (IgE)-mediated immunity. Levels of Fc⑀RI ␤ chain expression correlated with serum levels of total and antigen-specific IgE for HIV-1-negative car washers, but this was not the case for individuals coinfected with HIV-1. Overall, these data further implicate eosinophils as having a potential role in development of protective immunity against schistosomes and suggest that changes associated with HIV-1 coinfection increase susceptibility to reinfection.Schistosomes are parasitic trematodes responsible for causing disease in over 200 million people worldwide (14). A better understanding of the immunologic components involved in the development of protection against infection is needed to lay the foundation for the advancement of efficacious vaccines (49). A common finding in many studies is that a high concentration of serum parasite-specific immunoglobulin E (IgE) is related to resistance against schistosomes (6,12,13,27,39). However, whether IgE is directly involved in protective mechanisms in vivo has not been elucidated, as IgE exerts its effector function through Fc⑀RI-expressing cells. Several studies have demonstrated an association between eosinophilia and host protection against schistosomes (2, 18, 45), although whether eosinophils express the high-affinity IgE receptor remains under debate (1,3,4,17,21,23,26,40,42,43). Purified human eosinophils are cytotoxic to schistosomula in vitro in the presence of parasite-specific IgE, with eosinophils from helminthinfected individuals having greater potency (11,16,23,50). These observations suggest that IgE and eosinophils are likely to have an important role in host protection against schistosomes.Our laboratory is conducting a longitudinal study on Schistosoma mansoni infections in a cohort of adult male Kenyan car washers who are occupationally exposed to infective cercariae in the waters along the shores of Lake Victoria (22). Over 200 men in this group have been actively monito...

CD23-Bound IgE Augments and Dominates Recall Responses through Human Naive B Cells

“…ELISA plates were coated with 5 mg/ ml SWAP or 1 mg/ml dust mite Ag in PBS, and serum was evaluated for levels of Ag-specific IgE at a 1:10 dilution in 1% BSA/PBS (17). Sera was used as pooled dust mite-specific IgE high derived from uninfected/unexposed donors (n = 4 donors), SWAP-specific IgE high (n = 6 donors), or polyclonal IgE derived from uninfected/unexposed donors (n = 4 donors), which was not reactive for dust mite or SWAP, but had similar levels of total IgE as measured by ELISA (3500 6 520 ng/ml; Sigma-Aldrich/ SouthernBiotech).…”

Current Status of Vaccines for Schistosomiasis

“…There is also emerging evidence that schistosome infections may impact the etiology and transmission of human immunodeficiency virus/AIDS (HIV/AIDS) (22,23,72,73,80), tuberculosis (23,(42)(43)(44), and malaria (14,19,39,96,119,153), and vice versa. In particular, the possible interaction between schistosomiasis and HIV/ AIDS is receiving increasing attention, given the role of immune responses in both diseases and the geographic overlap in distribution; low CD4 ϩ T-cell counts resulting from HIV infection may increase susceptibility to schistosome infection and influence egg excretion (54,56,74). Thus, schistosomiasis imposes a high socioeconomic burden on many affected developing countries.…”

Association of Schistosomiasis and HIV Infection in Tanzania

“…Rhesus macaques with active S. mansoni infection were 17 times more susceptible to simian HIV (SHIV) acquisition after rectal inoculation than macaques without S. mansoni. 4 Although a variety of interactions between S. mansoni and HIV infection in humans have been described, [5][6][7][8][9][10] a direct association between active S. mansoni and HIV has not been documented in humans. If S. mansoni is a risk factor for HIV acquisition, this finding could have major implications for HIV prevention work in much of the world.…”