title: Phenotypic, morphological, and functional heterogeneity of splenic immature myeloid cells in the host response to tularemia.
abstract: Recent studies have linked accumulation of the Gr-1⁺ CD11b⁺ cell phenotype with functional immunosuppression in diverse pathological conditions, including bacterial and parasitic infections and cancer. Gr-1⁺ CD11b⁺ cells were the largest population of cells present in the spleens of mice infected with sublethal doses of the Francisella tularensis live vaccine strain (LVS). In contrast, the number of T cells present in the spleens of these mice did not increase during early infection. There was a significant delay in the kinetics of accumulation of Gr-1⁺ CD11b⁺ cells in the spleens of B-cell-deficient mice, indicating that B cells play a role in recruitment and maintenance of this population in the spleens of mice infected with F. tularensis. The splenic Gr-1⁺ CD11b⁺ cells in tularemia were a heterogeneous population that could be further subdivided into monocytic (mononuclear) and granulocytic (polymorphonuclear) cells using the Ly6C and Ly6G markers and differentiated into antigen-presenting cells following ex vivo culture. Monocytic, CD11b⁺ Ly6C(hi) Ly6G⁻ cells but not granulocytic, CD11b⁺ Ly6C(int) Ly6G⁺ cells purified from the spleens of mice infected with F. tularensis suppressed polyclonal T-cell proliferation via a nitric oxide-dependent pathway. Although the monocytic, CD11b⁺ Ly6C(hi) Ly6G⁻ cells were able to suppress the proliferation of T cells, the large presence of Gr-1⁺ CD11b⁺ cells in mice that survived F. tularensis infection also suggests a potential role for these cells in the protective host response to tularemia.
authors.affiliation: Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Rasmussen
authors.forename: Jason W
authors.initials: JW
authors.lastname: Tam
authors.forename: Nihal A
authors.initials: NA
authors.lastname: Okan
authors.forename: Patricio
authors.initials: P
authors.lastname: Mena
authors.forename: Martha B
authors.initials: MB
authors.lastname: Furie
authors.forename: David G
authors.initials: DG
authors.lastname: Thanassi
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Benach
authors.forename: Adrianus W M
authors.initials: AW
authors.lastname: van der Velden
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D039481:CD11b Antigen / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000472:pathogenicity*; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology* / Q000502:physiology*; D019707:Receptors, Chemokine / Q000032:analysis; D013154:Spleen / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D014406:Tularemia / Q000276:immunology* / Q000473:pathology*
chemical_list: D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine