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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

  • Microbial Genetics, Genomics and Molecular Biology
  • Published:
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Abstract

The severity of cryptococcosis in lupus from varying genetic-backgrounds might be different due to the heterogeneity of lupus-pathogenesis. This study explored cryptococcosis in lupus mouse models of pristane-induction (normal genetic-background) 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.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand

    Saowapha Surawut & Jiradej Makjaroen

  2. Inter-Department Program of Biomedical Sciences, Faculty of Graduate, Chulalongkorn University, Bangkok, Thailand

    Arthid Thim-uam

  3. Division of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Jutamas Wongphoom

  4. Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand

    Tanapat Palaga

  5. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Prapaporn Pisitkun

  6. Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Ariya Chindamporn & Asada Leelahavanichkul

  7. Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

    Asada Leelahavanichkul

Authors
  1. Saowapha Surawut
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  2. Jiradej Makjaroen
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  4. Jutamas Wongphoom
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  5. Tanapat Palaga
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  8. Asada Leelahavanichkul
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Correspondence to Asada Leelahavanichkul.

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Surawut, S., Makjaroen, J., Thim-uam, A. et al. 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. 57, 45–53 (2019). https://doi.org/10.1007/s12275-019-8311-8

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

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