title: Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4(+)CD25(+)Foxp3(+) Treg in mice.
abstract: Malaria and intestinal nematode infection are widespread and co-infection frequently occurs. We investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. Infection of C57BL/6 mice with Plasmodium yoelii 17XNL (Py) was transient and self-limiting, but preceding infection with Heligmosomoides polygyrus (Hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice. Co-infection with Hp led to reduced Py-responsive proliferation and IFN-gamma production of spleen cells, and higher activation of CD4(+)CD25(+)Foxp3(+) Treg. In vivo depletion of Treg recovered anti-Py immunity and rescued co-infected mice from exacerbated malaria. However, we did not observe any obvious ex vivo activation of Treg by either Hp products or living worms. Our results suggest that intestinal nematodes moderate host immune responses during acute malaria infection by aggressive activation of Treg. Elucidation of the mechanisms of Treg activation in situ is a target for future analyses.
authors.affiliation: Department of Parasitology, Kyushu University Graduate School of Medical Science, Fukuoka 812-0054, Japan. tetztani@gmail.com
authors.forename: Kohhei
authors.initials: K
authors.lastname: Tetsutani
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ishida
authors.forename: Liping
authors.initials: L
authors.lastname: Tu
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hamano
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Himeno
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000947:Antigens, Helminth / Q000276:immunology; D002452:Cell Count; D003208:Concanavalin A / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008288:Malaria / Q000150:complications / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009351:Nematospiroides dubius / Q000276:immunology*; D018512:Parasitemia; D010967:Plasmodium yoelii / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017206:Strongylida Infections / Q000150:complications / Q000276:immunology*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D003208:Concanavalin A; D007371:Interferon-gamma