title: The role of macrophages in the susceptibility of Fc gamma receptor IIb deficient mice to Cryptococcus neoformans.
abstract: Dysfunctional polymorphisms of FcγRIIb, an inhibitory receptor, are associated with Systemic Lupus Erythaematosus (SLE). Cryptococcosis is an invasive fungal infection in SLE, perhaps due to the de novo immune defect. We investigated cryptococcosis in the FcγRIIb-/- mouse-lupus-model. Mortality, after intravenous C. neoformans-induced cryptococcosis, in young (8-week-old) and older (24-week-old) FcγRIIb-/- mice, was higher than in age-matched wild-types. Severe cryptococcosis in the FcγRIIb-/- mice was demonstrated by high fungal burdens in the internal organs with histological cryptococcoma-like lesions and high levels of TNF-α and IL-6, but not IL-10. Interestingly, FcγRIIb-/- macrophages demonstrated more prominent phagocytosis but did not differ in killing activity in vitro and the striking TNF-α, IL-6 and IL-10 levels, compared to wild-type cells. Indeed, in vivo macrophage depletion with liposomal clodronate attenuated the fungal burdens in FcγRIIb-/- mice, but not wild-type mice. When administered to wild-type mice, FcγRIIb-/- macrophages with phagocytosed Cryptococcus resulted in higher fungal burdens than FcγRIIb+/+ macrophages with phagocytosed Cryptococcus. These results support, at least in part, a model whereby, in FcγRIIb-/- mice, enhanced C. neoformans transmigration occurs through infected macrophages. In summary, prominent phagocytosis, with limited effective killing activity, and high pro-inflammatory cytokine production by FcγRIIb-/- macrophages were correlated with more severe cryptococcosis in FcγRIIb-/- mice.
authors.affiliation: Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Saowapha
authors.initials: S
authors.lastname: Surawut
authors.affiliation: Medical Sciences Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Thunnicha
authors.initials: T
authors.lastname: Ondee
authors.affiliation: Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Sujittra
authors.initials: S
authors.lastname: Taratummarat
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.|Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Tanapat
authors.initials: T
authors.lastname: Palaga
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Prapaporn
authors.initials: P
authors.lastname: Pisitkun
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Ariya
authors.initials: A
authors.lastname: Chindamporn
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.|Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Bangkok, Thailand.
authors.forename: Asada
authors.initials: A
authors.lastname: Leelahavanichkul
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000473:pathology; D003453:Cryptococcosis / Q000401:mortality / Q000473:pathology* / Q000662:veterinary; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D004198:Disease Susceptibility; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000382:microbiology / Q000473:pathology / Q000662:veterinary; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics*; D012720:Severity of Illness Index; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C080571:Fc gamma receptor IIB; D015850:Interleukin-6; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha