Abstract
BackgroundIn rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites. A specific, balanced and, to an extent, protective immunity will develop over time in response to repeated parasite encounters, with immune responses initially being poorly adapted and non-protective. The cellular production of pro-inflammatory and regulatory cytokines and chemokines in response to helminth, protozoan antigens and ubiquitous allergens were studied in neonates, children, adults and the elderly.ResultsIn children schistosomiasis prevailed (33%) while hookworm and Entamoeba histolytica/E. dispar was found in up to half of adults and the elderly. Mansonella perstans filariasis was only present in adults (24%) and the elderly (25%). Two or more parasite infections were diagnosed in 41% of children, while such polyparasitism was present in 34% and 38% of adults and the elderly. Cytokine and chemokine production was distinctively inducible by parasite antigens; pro-inflammatory Th2-type cytokine IL-19 was activated by Entamoeba and Ascaris antigens, being low in neonates and children while IL-19 production enhanced “stepwise” in adults and elderly. In contrast, highest production of MIP-1delta/CCL15 was present in neonates and children and inducible by Entamoeba-specific antigens only. Adults and the elderly had enhanced regulatory IL-27 cytokine responses, with Th2-type chemokines (MCP-4/CCL13, Eotaxin-2/CCL24) and cytokines (IL-33) being notably inducible by helminth- and Entamoeba-specific antigens and fungus-derived allergens. The lower cellular responsiveness in neonates and children highlighted the development of a parasite-specific cellular response profile in response to repeated episodes of exposure and re-infection.ConclusionsFollowing repeated exposure to parasites, and as a consequence of host inability to prevent or eliminate intestinal helminth or protozoa infections, a repertoire of immune responses will evolve with lessened pro-inflammatory and pronounced regulatory cytokines and chemokines; this is required for partial parasite control as well as for preventing inadequate and excessive host tissue and organ damage.
Highlights
In rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites
With chronic helminth parasite infections Th2-type cytokine responses predominate [5], while Th1-type cytokine responses are important for protection against protozoa, e.g. amoebiasis [6] or Plasmodium falciparum malaria [7]
In order to further clarify the extent to which these immune mediators become activated or suppressed during early life parasite exposure, and with a view to later life chronic pathogen persistence, we studied the cellular production of pro-inflammatory and regulatory cytokines and chemokines in neonates, children, adults, and the elderly in response to helminth and protozoa infectious challenge and to ubiquitous allergen exposure
Summary
In rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites. The cellular production of pro-inflammatory and regulatory cytokines and chemokines in response to helminth, protozoan antigens and ubiquitous allergens were studied in neonates, children, adults and the elderly. Two billion people are infected with helminth parasites worldwide, and some intestinal parasites may affect up to 70% of an endemic population [2]. The encounter with parasite species elicits distinct and specific immune responses in their host; cytokines and chemokines are key players which regulate and polarize cellular reactivity and antibody responses to antigens and allergens. With chronic helminth parasite infections Th2-type cytokine responses predominate [5], while Th1-type cytokine responses are important for protection against protozoa, e.g. amoebiasis [6] or Plasmodium falciparum malaria [7]
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