title: Cryptococcus gattii infection dampens Th1 and Th17 responses by attenuating dendritic cell function and pulmonary chemokine expression in the immunocompetent hosts.
abstract: Cryptococcal infections are primarily caused by two related fungal species: Cryptococcus neoformans and Cryptococcus gattii. It is well known that C. neoformans generally affects immunocompromised hosts; however, C. gattii infection can cause diseases in not only immunocompromised hosts but also immunocompetent individuals. While recent studies suggest that C. gattii infection could dampen pulmonary neutrophil recruitment and inflammatory cytokine production in immunocompetent hosts, the impact of C. gattii infection on the development of their adaptive T helper cell immune response has not been addressed. Here, we report that C. neoformans infection with highly virulent and less virulent strains preferentially induced pulmonary Th1 and Th17 immune responses in the host, respectively. However, fewer pulmonary Th1 and Th17 cells could be detected in mice infected with C. gattii strains. Notably, dendritic cells (DC) in mice infected with C. gattii expressed much lower levels of surface MHC-II and Il12 or Il23 transcripts and failed to induce effective Th1 and Th17 differentiation in vitro. Furthermore, the expression levels of Ip10 and Cxcl9 transcripts, encoding Th1-attracting chemokines, were significantly reduced in the lungs of mice infected with the highly virulent C. gattii strain. Thus, our data suggest that C. gattii infection dampens the DC-mediated effective Th1/Th17 immune responses and downregulates the pulmonary chemokine expression, thus resulting in the inability to mount protective immunity in immunocompetent hosts.
authors: Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand Graduate Program in Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand upornpim@tu.ac.th.
authors: Pornpimon
authors: P
authors: Angkasekwinai
authors: Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand Graduate Program in Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
authors: Nuntarat
authors: N
authors: Sringkarin
authors: Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
authors: Oratai
authors: O
authors: Supasorn
authors: Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
authors: Madtika
authors: M
authors: Fungkrajai
authors: Division of Allergy and Immunology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Yui-Hsi
authors: YH
authors: Wang
authors: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Methee
authors: M
authors: Chayakulkeeree
authors: Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Popchai
authors: P
authors: Ngamskulrungroj
authors: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Nasikarn
authors: N
authors: Angkasekwinai
authors: Center of Excellence for Flow Cytometry, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Kovit
authors: K
authors: Pattanapanyasat
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology*; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology; D056285:Cryptococcus gattii / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology
chemical_list: D018925:Chemokines