Cellular responses and cytokine production in post-treatment hookworm patients from an endemic area in Brazil

Abstract

SUMMARYHuman hookworm infections are distributed widely in tropical areas and have a significant impact on host morbidity and human health. In the present study, we investigated the cellular responsiveness and cytokine production in peripheral blood mononuclear cells (PBMC) from Necator americanus-infected schoolchildren who had recently received chemotherapy, and compared them with non-infected endemic controls. Hookworm patients and treated, egg-negative individuals showed a lower cellular reactivity against phytohaemagglutinin (PHA) and hookworm antigen when compared with eggnegative endemic controls. The baseline production of proinflammatory tumour necrosis factor-a (TNFa ) in PBMC from infected patients and treated, egg-negative individuals was elevated. On the other hand, PHA-or hookworm antigen-induced interleukin (IL)-12 and interferon (IFN)-g secretion was higher in endemic controls than in hookworm patients, who either continued egg-positive or were eggnegative after treatment. Also, PBMC from endemic controls secreted more IL-5 and IL-13 than the other patient groups. Opposite to that, the spontaneous as well as the antigen-driven IL-10 secretion was lower in endemic controls when compared with the other groups. In summary, patently hookworminfected as well as egg-negative treated patients disclosed an elevated spontaneous cellular secretion of proinflammatory TNF-a , a prominent secretion of regulatory Th2-type IL-10 and an impaired production of IL-12, IFN-g , IL-5 and IL-13.

Binding of Excreted and/or Secreted Products of Adult Hookworms to Human NK Cells inNecator americanus-Infected Individuals from Brazil

“…Our studies demonstrated that neither the presence of IL-10 nor that of TGF-␤ altered the capacity of NK cells from egg-negative individuals to bind ES products, suggesting that these cytokines have little impact on receptors for NKBP interaction. These observations are further supported by the findings of Geiger et al (15,16), showing that high levels of IL-10 are present in all individuals resident in areas of hookworm endemicity. Despite the presence of elevated IL-10 in egg-negative individuals from areas of endemicity, their NK cells were clearly not affected in their capacity to interact with Necator ES products (Fig.…”

“…The second mechanism that we considered to explain the impaired interaction of ES products with NK cells from Necator-infected individuals was the presence of IL-10, a well-established immunomodulator during chronic helminth infections (4,27). As reported by Geiger et al (15,16), IL-10 is highly elevated in individuals resident in areas of Necator transmission. To determine whether IL-10 might have the capacity to affect receptors important for binding of NK cells to ES products, we conducted in vitro binding experiments in which NK cells from egg-negative individuals were incubated for up to 72 h with different doses of IL-10 (1 to 125 ng/ml) prior to interaction with bioES.…”

“…However, our antibody preblocking studies suggest that decreased expression of these two markers is unlikely to be responsible for a lack of NKPB binding. We also explored the possibility that immunoregulatory cytokines, such as IL-10 and TGF-␤, which are documented to be elevated in individuals from areas of Necator endemicity (15,16) and are known regulators of receptor expression on circulating leukocytes (27), might affect NKBP receptor expression. Our studies demonstrated that neither the presence of IL-10 nor that of TGF-␤ altered the capacity of NK cells from egg-negative individuals to bind ES products, suggesting that these cytokines have little impact on receptors for NKBP interaction.…”

Relationship between Mycobacterium Tuberculosis and Hookworm Infections among School Children in Mbita, Kenya

“…+ regulatory T cells [23] and repeated infection with hookworm stimulates production of high levels of IL-10 [24], which inhibits host protective immunity against M. tuberculosis. Accordingly, there is a possibility that hookworm-induced IL-10 impacts on the sensibility to M. tuberculosis infection.…”

Geohelminth infections: a review of the role of IgE and assessment of potential risks of anti‐IgE treatment

“…Children living in endemic areas of Brazil and who appear to be resistant to hookworm infection produce greater levels of both type-1 (IFN-c) and type-2 cytokines compared with chronically infected children (20), and a treatment study of infected adults from a highly endemic area of Papua New Guinea provided evidence that resistance to reinfection following treatment was associated with the type-2 cytokine, IL-5 (21). Together these data indicate a potential role for both type-1 and type-2 cytokinemediated mechanisms in protective immunity.…”