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.

The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P < 0.05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

During human schistosomiasis host responses to antigens of various parasite life-cycle stages may contribute to whether the severe, hepatosplenic state develops or the patient remains relatively asymptomatic throughout infection, and may play a role in resistance. This study evaluated production of interferon gamma (IFN-gamma) in vitro by schistosome antigen-stimulated peripheral blood mononuclear cells (PBMCs) from asymptomatic patients, and by PBMCs from apparently uninfected, untreated persons living in areas endemic for Schistosoma mansoni ('endemic normals'). IFN-gamma production parallels PBMC proliferation in that schistosomal egg antigens stimulate patent patients' cells poorly, but strongly stimulate PBMCs from 'endemic normals'. This is proportionally true for antigens from adult worms and cercariae. Although asymptomatic patent patients' cells produced little or no IFN-gamma in response to the 3 schistosomal antigenic extracts, their PBMCs, and PBMCs from 'endemic normals', produced expected amounts of IFN-gamma when exposed to phytohaemagglutinin. This implies that persons with patent infections have schistosome antigen-specific defects in their ability to respond to IFN-gamma production that are not exhibited by putatively resistant 'endemic normals'.

Abstract. Cellular and humoral immune responses to Schistosoma mansoni antigen preparations were evaluated in individuals presumed to be susceptible or resistant to reinfection after chemotherapeutic cure. A consistent proliferative increase in the response to soluble egg antigen (SEA) was observed post-treatment in both the susceptible and resistant groups. However, this change was not related to resistance. Isotype studies showed that IgM antibody levels to soluble worm antigen preparation (SWAP) and cercariae antigens were significantly higher in the resistant group than in the susceptible group. Post-treatment, an increase in IgE anti-SWAP and anti-schistosomular tegument (STEG) responses and a decrease in IgG4 anti-SEA and anti-STEG responses were observed in the resistant group. These finding are similar to those we have reported previously for a putative resistant group termed endemic normals, and are compatible with immunologic studies in different endemic areas. Together, these findings indicate that even on the population level, high IgE specificities coupled with low IgG4 specificities correlate well with documented resistance to reinfection.Based on field studies following curative chemotherapy of either Schistosoma mansoni 1-3 or S. haematobium, 4,5 individuals are often categorized as being either susceptible or resistant to natural reinfection by schistosomes. These studies have shown that resistance to reinfection is an age-related phenomenon, with most people in endemic areas becoming resistant, or expressing their resistance during their second decade of life. When determined directly or by estimation, resistance appears to be unrelated to the degree of contact that the susceptible and resistant groups have with cercariaecontaining water, and is usually attributed to immunity rather than physiologic or behavioral changes with age. 4,6,7 These studies have cataloged a variety of humoral immune responses, and are in agreement with several of the correlations demonstrated between given immune responses and susceptible or resistant groups. 8,9 A number of studies have shown associations between resistance status and a balance between the level of effective anti-schistosomula antibodies and the presence of blocking antibodies. 5,[10][11][12] The latter are sometimes most easily demonstrated as antibodies to egg antigens that cross-react with epitopes present in the schistosomula tegument. 3,10The most common features that show relationships to resistance to reinfection include high levels of IgE against adult worm or larval antigens, while high levels of IgG4 and IgM antibodies against egg antigens generally parallel susceptibility. 5,9,[11][12][13][14][15] Recent studies have also reported correlations between resistance and elevated levels of IgA against a schistosome vaccine candidate (Sm 28 glutathione-S-transferase). 16,17 Further studies with other antigens have demonstrated that higher levels of IgE against a 22-kD schistosomula moiety 9 and higher levels of IgM against a 68-kD adult schistos...

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The isotypic patterns of antibodies against Schistosoma mansoni antigenic preparations from eggs (SEA), adult worms (SWAP) and cercariae (CERC) have been studied in sera from two groups of individuals living in an area endemic for S. mansoni. One of the groups was comprised of individuals diagnosed as having S. mansoni infections based on their patency, i.e. those passing eggs in their faeces (patent infections, PI). The other group has been consider 'putatively resistant' due to their residence in an endemic area, their documented exposure to positive transmission sites, and their repeated negativity upon stool examinations (endemic normals, EN). There are strong specific responses of IgG1, IgG4 and IgM, particularly to SEA and CERC, by both groups. The reactivities of all isotypes were lower to SWAP. The responses of IgG4, IgM and IgE anti-CERC in EN and PI are higher than those found in normal individuals from outside endemic areas. In general, EN individuals express a relative higher level of anti-STEG IgE as compared to IgG4. On the other hand the pool of sera from PI showed the opposite pattern of higher IgG4 as compared to IgE. Several correlations are seen between isotypic responses to SEA, SWAP and CERC based on comparisons to the anti-SWAP IgE responses of the individuals in the two groups. These comparisons indicate the presence of distinct immunologic differences between individuals in the PI and the EN groups.

BackgroundHookworms survive for several years (5 to 7 years) in the host lumen, inducing a robust but largely ineffective immune response. Among the most striking aspects of the immune response to hookworm (as with many other helminths) is the ablation of parasite-specific T cell proliferative response (hyporesponsiveness). While the role of the adaptive immune response in human helminth infection has been well investigated, the role of the innate immune responses (e.g., dendritic cells and eosinophils) has received less attention and remains to be clearly elucidated.Methodology/Principal FindingsWe report on the differentiation/maturation of host dendritic cells in vitro and the eosinophil activation/function associated with human hookworm infection. Mature DCs (mDCs) from Necator americanus (Necator)–infected individuals showed an impaired differentiation process compared to the mDCs of non-infected individuals, as evidenced by the differential expression of CD11c and CD14. These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR. The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected–derived mDCs was further evidenced by their reduced ability to induce cell proliferation. We also showed that this alternative DC differentiation is partially induced by excreted-secreted hookworm products. Conversely, eosinophils from the same individuals showed a highly activated status, with an upregulation of major cell surface markers. Antigen-pulsed eosinophils from N. americanus–infected individuals induced significant cell proliferation of autologous PBMCs, when compared to non-infected individuals.ConclusionChronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the ablation of the parasite-specific T cell proliferative response. Interestingly, a concomitant upregulation of the major cell surface markers of eosinophils was observed in hookworm-infected individuals, indicative of antigen-specific immune responses, especially antigen presentation. We showed that in addition to the postulated role of the eosinophils as effector cells against helminth infection, activated cells may also be recruited to sites of inflammation and contribute to the immune response acting as antigen presenting cells.

In this transversal study, factors related to infection with and transmission of