Cytokine and chemokine responses to helminth and protozoan parasites and to fungus and mite allergens in neonates, children, adults, and the elderly

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.

Chemokine levels and parasite- and allergen-specific antibody responses in children and adults with severe or uncomplicatedPlasmodium falciparummalaria

“…With repeated exposure to Plasmodium spp. and immune maturation, adequate and regulatory cytokine and chemokine responses may set off cellular effector mechanisms which will not induce severe infl ammation and which will avoid excessive host tissue and organ damage [16]. Recent stud-ies have shown that, in children with P. falciparum malaria, the profi le of cytokine and chemokine levels varied with disease severity; moreover, the proinfl ammatory chemokines MIP-1α/CCL3, MIP-1β/CCL4, and MIG/ CXCL9 and cytokines IL-31 and IL-33 were elevated, while RANTES/CCL5 and IL-27 appeared suppressed in children with severe falciparum malaria [17,18].…”

Cellular cytokine and chemokine responses to parasite antigens and fungus and mite allergens in children co-infected with helminthes and protozoa parasites

“…In the present study none of the participating children was infected with Ascaris lumbricoides and it should be considered that hookworm and S. haematobium and S. mansoni infections will cause intestinal and urinary tract tissue damage resulting in bloody urines and mostly occult blood in stools; these helminthes will always cause gastrointestinal inflammation. As previously observed, in infants and children with helminth and protozoa infections regulatory cytokine and chemokine responses were not evolved to levels as observed in adults [ 40 ], and such immune response profiles may develop with ageing and repeated episodes of exposure and persistent parasite infections. In the present study, allergen-specific positive skin prick test (SPT) responses were more frequent in co-infected children than in infection-free pupils suggesting that parasite co-infections may have triggered or even amplified pro-inflammatory reactivity to allergens.…”

Successful long-term maintenance of Mansonella perstans in an in vitro culture system

“…Interestingly M. perstans is, however, considered one of the most prevalent human diseases in tropical areas with approximately 114 million infected people [ 1 , 2 , 18 ]. Most of the knowledge about M. perstans infection has been obtained as a by-product of studies with other filarial or parasitic infections [ 19 – 22 ] that were considered to be more important for public health. However, M. perstans -induced symptoms such as subcutaneous swellings, abdominal pain, skin rashes, pericarditis and pleuritis [ 1 , 2 ] have been reported.…”