Cytokine and chemokine responses in patients co-infected with Entamoeba histolytica/dispar, Necator americanus and Mansonella perstans and changes after anti-parasite treatment.
This study examined the impact of concurrent parasite infections (amoebiasis, filariasis, necatoriasis) and the effect of anti-parasite treatment on cytokine and chemokine responses in singly and poly-parasitized patients. Cellular reactivity and parasite-specific Th1- and Th2-type cytokine and chemokine profiles were investigated before and six weeks after treatment. In those patients infected with three parasite species, cellular secretion of interleukin 5 (IL-5) and IL-12p40 by PBMC was strongly diminished (p<0.005) but IL-10 was elevated in parasite-infected patients (p<0.0001) in response to protozoa- and helminth-specific as well as bacteria-specific antigens. Macrophage inflammatory chemokines (MIP-1alpha/CCL3 and MIP-1beta/CCL4), macrophage-derived chemokine (MDC/CCL22) and neutrophil activating chemokine (IL-8/CXCL8) were produced by PBMC in similar amounts in endemic controls and singly and poly-parasitized patients, but thymus and activation-regulated chemokine (TARC/CCL17) was produced the highest by PBMC from patients with triple parasite infections (p<0.0001). Following anti-parasite therapy, secretion of IL-12p40 and IL-5 augmented significantly in treated patients while IL-10, MDC, MIP-1alpha, TARC and IL-8 substantially diminished (all p<10(-5)) when their PBMC were activated with parasite- and bacteria-specific antigens. In summary, PBMC from poly-parasitized patients responded to protozoa- and helminth-specific antigens with a compromised IL-5 and IL-12p40 but high IL-10 and a substantial chemokine release. Chemokines may attract and activate effector cells in peri-parasitic tissues to limit parasite proliferation and dissemination, while depressed IL-5 and IL-12p40 but prominent IL-10 may prevent eosinophil and cytotoxic cell-mediated inflammatory processes and pathogenesis to the host. The changes in this profile following anti-parasite therapy disclosed the dynamics of an immune adaptation associated with parasite accumulation and also with clearance of parasite infections.
Soboslay
Peter T
PT
Institute for Tropical Medicine, Wilhelmstr. 27, University of Tübingen, Germany. peter.soboslay@uni-tuebingen.de
Hamm
David M
DM
Pfäfflin
Frieder
F
Fendt
Julia
J
Banla
Meba
M
Schulz-Key
Hartwig
H
D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000097:blood; D018925:Chemokines / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004749:Entamoebiasis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008368:Mansonelliasis / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D017221:Necator americanus; D009332:Necatoriasis / Q000188:drug therapy / Q000378:metabolism*
D000871:Anthelmintics; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018925:Chemokines; D016207:Cytokines