Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4(+)CD25(+)Foxp3(+) Treg in mice.
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.
Tetsutani
Kohhei
K
Department of Parasitology, Kyushu University Graduate School of Medical Science, Fukuoka 812-0054, Japan. tetztani@gmail.com
Ishiwata
Kenji
K
Ishida
Hidekazu
H
Tu
Liping
L
Torii
Motomi
M
Hamano
Shinjiro
S
Himeno
Kunisuke
K
Hisaeda
Hajime
H
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
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