title: Intestinal helminth infection impacts the systemic distribution and function of the naive lymphocyte pool.
abstract: Homeostasis is a fundamental principle of biological systems. A paradigm of immune homeostasis is the remarkably constant number of naive T and B lymphocytes in the body that continuously circulate through the secondary lymphoid organs to maximize immune surveillance. Whether the dynamics and distribution of the systemic naive lymphocyte pool is affected following organ-specific infection is not known. Here we show that, following infection of mice with an enteric helminth, naive T and B lymphocytes accumulate in the T helper type 2-reactive mesenteric lymph node while they are concurrently depleted from non-draining peripheral lymph nodes. This systemic redistribution of naive lymphocytes is sustained into the chronic phase of the infection, requires lymphotoxin beta receptor-dependent signals and is associated with a reduced ability of parasitized animals to mount antigen-specific cellular and humoral immune responses to heterologous immunization or infection at peripheral sites. Our data suggest that the function of the homeostatic naive lymphocyte pool can be modulated by its systemic distribution following infection and may provide a novel concept underlying compromised immune responsiveness at peripheral sites in helminth-infected individuals.
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: I L
authors.initials: IL
authors.lastname: King
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mohrs
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: A P
authors.initials: AP
authors.lastname: Meli
authors.affiliation: Department of Pathology, Meakins-Christie Laboratories, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Downey
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lanthier
authors.affiliation: Department of Medicine, Meakins-Christie Laboratories, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Tzelepis
authors.affiliation: Department of Microbiology and Immunology, Department of Physiology, Complex Traits Group, McGill University, Montreal, Quebec, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Fritz
authors.affiliation: Department of Microbiology and Immunology, University of Texas School of Medicine Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Tumanov
authors.affiliation: Department of Pathology, Meakins-Christie Laboratories, McGill University Health Centre, Montreal, Quebec, Canada.|Department of Medicine, Meakins-Christie Laboratories, McGill International TB Centre, McGill University Health Centre, Montreal, Quebec, Canada.|Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Divangahi
authors.affiliation: Department of Microbiology and Immunology, University of Texas School of Medicine Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Leadbetter
authors.affiliation: Trudeau Institute, Saranac Lake, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mohrs
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006373:Helminthiasis / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000469:parasitology; D053259:Lymphotoxin beta Receptor / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009351:Nematospiroides dubius / Q000276:immunology*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology
chemical_list: D053259:Lymphotoxin beta Receptor