Title |
Increased susceptibility against Cryptococcus neoformans of lupus mouse models (pristane-induction and FcGRIIb deficiency) is associated with activated macrophage, regardless of genetic background |
Author |
Saowapha Surawut1, Jiradej Makjaroen1, Arthid Thim-uam2, Jutamas Wongphoom3, Tanapat Palaga4, Prapaporn Pisitkun5, Ariya Chindamporn6, and Asada Leelahavanichkul6,7* |
Address |
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, Thailand |
Bibliography |
Journal of Microbiology, 57(1),45–53, 2019,
|
DOI |
10.1007/s12275-019-8311-8
|
Key Words |
Cryptococcus neoformans, pristane model, FcGRIIb
deficient mice, lupus, susceptibility, murine model |
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. |