title: Primary Heligmosomoides polygyrus bakeri infection induces myeloid-derived suppressor cells that suppress CD4+Th2 responses and promote chronic infection.
abstract: Primary infection with the gastrointestinal nematode Heligmosomoides polygyrus bakeri is chronic in C57BL/6 (B6) mice whereas challenge infection is rapidly eliminated. F4/80-CD11b+Gr+cells, presumed to be neutrophils, were reported to accumulate around encysting larvae in intestinal tissue during primary infection, but their exact identity and role remain unclear. We observed significant increases in F4/80-CD11bhiGr1hicells in mesenteric lymph nodes (MLNs) and spleen after primary but not challenge infection; a high proportion of these cells expressed Ly6G and Ly6C. These cells, which phenotypically resemble myeloid-derived suppressor cells (MDSC), increased in lamina propria (LP) early during primary infection. Increased MDSC were associated with low numbers of alternatively activated macrophages (AAMØ) in LP and CD4+GATA3+T cells and AAMØ in MLN and spleen. Purified CD11c-CD11b+Gr1+cells from H. polygyrus bakeri-infected mice suppressed OVA-specific CD4+T-cell proliferation via a nitric oxide-dependent mechanism and parasite-specific IL-4 secretion in vitro. Adoptive transfer of CD11c-CD11b+Gr1+cells from mice with primary infection resulted in significantly higher adult worm burdens and increased egg production in naïve B6 recipients infected with H. polygyrus bakeri. Altogether, these findings indicate that primary H. polygyrus bakeri infection induces a novel subset of MDSC that suppress CD4+Th2 responses and promote chronic infection.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Valanparambil
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Tam
authors.affiliation: Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Jardim
authors.affiliation: Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.|Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: T G
authors.initials: TG
authors.lastname: Geary
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.|Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.|Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: M M
authors.initials: MM
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000469:parasitology; D009351:Nematospiroides dubius / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology; D059208:Parasite Load; D017206:Strongylida Infections / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology
chemical_list: D000947:Antigens, Helminth; D015847:Interleukin-4