Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs
Autor: | Atsushi Tamura, Koya Suzuki, Kotone Kawamura, Jun Kasamatsu, Tong Zong, Kazuyoshi Kawakami, Hideki Yamamoto, Yuki Kitai, Hiroshi Kiyonari, Tomomitsu Miyasaka, Daiki Tanno, Sachiko Tsukita, Keiko Ishii, Aki Shiraishi, Hiromasa Tanno, Ko Sato, Ikumi Matsumoto, Anna Miyahara, Takafumi Kagesawa, Akiho Oniyama, Aya Umeki, Emi Kanno |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
CD4-Positive T-Lymphocytes
Science Immunology Cryptococcus Microbiology Airborne transmission Article Interferon-gamma Mice medicine Animals Respiratory system Claudin Lung Mice Knockout Multidisciplinary medicine.diagnostic_test biology Tight junction Meningoencephalitis Cryptococcosis Pneumonia biology.organism_classification medicine.disease Bronchoalveolar lavage medicine.anatomical_structure Cellular Microenvironment Organ Specificity Claudins Medicine |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Cryptococcus deneoformans is an opportunistic fungal pathogen that infects the lungs via airborne transmission and frequently causes fatal meningoencephalitis. Claudins (Cldns), a family of proteins with 27 members found in mammals, form the tight junctions within epithelial cell sheets. Cldn-4 and 18 are highly expressed in airway tissues, yet the roles of these claudins in respiratory infections have not been clarified. In the present study, we analyzed the roles of Cldn-4 and lung-specific Cldn-18 (luCldn-18) in host defense against C. deneoformans infection. luCldn-18-deficient mice exhibited increased susceptibility to pulmonary infection, while Cldn-4-deficient mice had normal fungal clearance. In luCldn-18-deficient mice, production of cytokines including IFN-γ was significantly decreased compared to wild-type mice, although infiltration of inflammatory cells including CD4+ T cells into the alveolar space was significantly increased. In addition, luCldn-18 deficiency led to high K+ ion concentrations in bronchoalveolar lavage fluids and also to alveolus acidification. The fungal replication was significantly enhanced both in acidic culture conditions and in the alveolar spaces of luCldn-18-deficient mice, compared with physiological pH conditions and those of wild-type mice, respectively. These results suggest that luCldn-18 may affect the clinical course of cryptococcal infection indirectly through dysregulation of the alveolar space microenvironment. |
Databáze: | OpenAIRE |
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