Immune Responses in Human Necatoriasis: Association between Interleukin‐5 Responses and Resistance to Reinfection

Abstract

Cytokine and proliferative responses to Necator americanus infection were measured in a treatment-reinfection study of infected subjects from an area of Papua New Guinea where N. americanus is highly endemic. Before treatment, most subjects produced detectable interleukin (IL)-4 (97%), IL-5 (86%), and interferon (IFN)- gamma (64%) in response to adult N. americanus antigen. Pretreatment IFN- gamma responses were negatively associated with hookworm burden, decreasing by 18 pg/mL for each increase of 1000 eggs/gram (epg) (n=75; P<.01). Mean IFN- gamma responses increased significantly after anthelmintic treatment, from 166 to 322 pg/mL (n=42; P<.01). The intensity of reinfection was significantly negatively correlated with pretreatment IL-5 responses, decreasing by 551 epg for each 100 pg/mL increase in production of IL-5 (n=51; P<.01). These data indicate that there is a mixed cytokine response in necatoriasis, with worm burden-associated suppression of IFN- gamma responses to adult N. americanus antigen. Resistance to reinfection is associated with the parasite-specific IL-5 response.

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

“…In support of this, we observed that NK cells isolated from Necator-infected patients and cultured directly ex vivo without further stimulation expressed significantly higher intracellular levels of IFN-␥ than NK cells from egg-negative individuals from both areas of endemicity and areas of nonendemicity, suggesting that these cells could have been primed to secrete IFN-␥ in vivo. Previous studies examining cytokine profiles in individuals infected with hookworms have shown a "mixed" cytokine production profile that includes the presence of IFN-␥ (15,16,28,29). Our findings that N. americanus ES products have the capacity to induce NK cell recruitment fits well with the idea that NK cells might be actively recruited by adult worms during infection, enabling them to interact with and be activated by ES products in situ.…”

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

“…For example, Th2-dependent eosinophilic pneumonia is frequently observed after infection with a significant number of helminths, such as filaria, hookworm, or A. lumbricoides. However, some reports have shown that T helper 1 (Th1), rather than Th2 cytokines, are produced from PBMCs derived from hookworm infected-individuals in endemic areas [15][16][17]. In endemic areas, people are frequently exposed to pathogens that induce a Th1 response before or after they are infected with helminths, which may be the reason why Th2 immune responses appear dampened, even in those co-infected with helminthes.…”

Haemonchus contortus(Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response

“…Protective immunity against these parasites is largely dependant on the activation of CD4+ T helper cells and on the Th 2 polarization of the immune response [35], while a Th 1 response is associated with the survival of these parasites and increased host susceptibility to infection [13,14]. In humans, the protective immune response observed in natural Ascaris lumbricoïdes or Necator americanus infections is similarly associated with a high Th 2 -type cytokine polarization [11,26]. In ruminants, the nature of the immune response towards gastrointestinal helminths is less clear and the existence of a true Th 1 /Th 2 dichotomy was questioned in the late nineties [9,15,24].…”