Increased susceptibility against Cryptococcus neoformans of lupus mouse models (pristane-induction and FcGRIIb deficiency) is associated with activated macrophage, regardless of genetic background

Saowapha Surawut; Jiradej Makjaroen; Arthid Thim-uam; Jutamas Wongphoom; Tanapat Palaga; Prapaporn Pisitkun; Ariya Chindamporn; Asada Leelahavanichkul

doi:10.1007/s12275-019-8311-8

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Increased susceptibility against Cryptococcus neoformans of lupus mouse models (pristane-induction and FcGRIIb deficiency) is associated with activated macrophage, regardless of genetic background: Saowapha Surawut ¹, Jiradej Makjaroen ¹, Arthid Thim-uam ², Jutamas Wongphoom ³, Tanapat Palaga ⁴, Prapaporn Pisitkun ⁵, Ariya Chindamporn ⁶, Asada Leelahavanichkul ^6,7; Journal of Microbiology 2019;57(1):45-53.
DOI: https://doi.org/10.1007/s12275-019-8311-8
Published online: November 19, 2018

¹Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand, ²Inter-Department Program of Biomedical Sciences, Faculty of Graduate, Chulalongkorn University, Bangkok, Thailand, ³Division of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, ⁴Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand, ⁵Division of Allergy, Immunology and Rheumatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, ⁶Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, ⁷Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand¹Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand, ²Inter-Department Program of Biomedical Sciences, Faculty of Graduate, Chulalongkorn University, Bangkok, Thailand, ³Division of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, ⁴Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand, ⁵Division of Allergy, Immunology and Rheumatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, ⁶Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, ⁷Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

Corresponding author: Asada Leelahavanichkul , Tel: +66-2-256-4132;,

Received: 14 June 2018 • Revised: 17 August 2018 • Accepted: 6 September 2018

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Abstract

The severity of cryptococcosis in lupus from varying geneticbackgrounds might be different due to the heterogeneity of lupus-pathogenesis. This study explored cryptococcosis in lupus mouse models of pristane-induction (normal geneticbackground) and FcGRIIb deficiency (genetic defect). Because the severity of lupus nephritis, as determined by proteinuria and serum creatinine, between pristane and FcGRIIb-/- mice were similar at 6-month-old, Cryptococcus neoformans was intravenously administered in 6-month-old mice and were age-matched with wild-type. Indeed, the cryptococcosis disease severity, as evaluated by mortality rate, internal-organ fungal burdens and serum cytokines, between pristane and FcGRIIb-/- mice was not different. However, the severity of cryptococcosis in wild-type was less severe than the lupus mice. On the other hand, phagocytosis activity of peritoneal macrophages from lupus mice (pristane and FcGRIIb-/-) was more predominant than the wild-type without the difference in macrophage killing-activity among these groups. In addition, the number of active T helper cells (Th-cell) in the spleen, including Th-cells with intracellular IFN-γ, from lupus mice (pristane and FcGRIIb-/-) was higher than wildtype. Moreover, these active Th-cells were even higher after 2 weeks of cryptococcal infection. These data support enhanced macrophage activation through prominent Th-cells in both lupus models. In conclusion, an increased susceptibility of cryptococcosis in both lupus models was independent to genetic background. This might due to Th-cell enhanced macrophage phagocytosis with the interference of macrophage killing activity from Cryptococcal immune-evasion properties.

Keywords: Cryptococcus neoformans;pristane model;FcGRIIb deficient mice;lupus;susceptibility;murine model

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Increased susceptibility against Cryptococcus neoformans of lupus mouse models (pristane-induction and FcGRIIb deficiency) is associated with activated macrophage, regardless of genetic background

J. Microbiol. 2019;57(1):45-53. Published online November 19, 2018

DOI: https://doi.org/10.1007/s12275-019-8311-8

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