Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium
Abstract The programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. How...
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Nature Portfolio
2021
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oai:doaj.org-article:56971edd017d426bbeae3d06975f937a2021-12-02T17:19:16ZDepletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium10.1038/s41598-021-97391-42045-2322https://doaj.org/article/56971edd017d426bbeae3d06975f937a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97391-4https://doaj.org/toc/2045-2322Abstract The programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the effect of blocking this pathway in pulmonary Mycobacterium avium–intracellulare complex (MAC) infection is not fully understood. Wild-type, PD-1-deficient mice, and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in MAC-infected mice. However, marked infiltration of CD8-positive T lymphocytes was observed in the lungs of PD-1 and PD-L1-deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8-positive T cells and related chemokine activity were upregulated in the infected lungs of PD-1 and PD-L1-deficient mice. Thus, the lack of change in susceptibility to MAC infection in PD-1 and PD-L1-deficient mice might be explained by the absence of obvious changes in the Th1 immune response. Furthermore, activated CD8-positive cells in response to MAC infection in these mice seemed to not be relevant in the control of MAC infection.Masayuki NakajimaMasashi MatsuyamaMio KawaguchiSosuke MatsumuraTakumi KiwamotoYosuke MatsunoYuko MorishimaKazufumi YoshidaMingma Thsering SherpaKai YazakiRyota TanakaNaoko OkiyamaMasafumi MurataniYukio IshiiNobuyuki HizawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Masayuki Nakajima Masashi Matsuyama Mio Kawaguchi Sosuke Matsumura Takumi Kiwamoto Yosuke Matsuno Yuko Morishima Kazufumi Yoshida Mingma Thsering Sherpa Kai Yazaki Ryota Tanaka Naoko Okiyama Masafumi Muratani Yukio Ishii Nobuyuki Hizawa Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium |
| description |
Abstract The programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the effect of blocking this pathway in pulmonary Mycobacterium avium–intracellulare complex (MAC) infection is not fully understood. Wild-type, PD-1-deficient mice, and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in MAC-infected mice. However, marked infiltration of CD8-positive T lymphocytes was observed in the lungs of PD-1 and PD-L1-deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8-positive T cells and related chemokine activity were upregulated in the infected lungs of PD-1 and PD-L1-deficient mice. Thus, the lack of change in susceptibility to MAC infection in PD-1 and PD-L1-deficient mice might be explained by the absence of obvious changes in the Th1 immune response. Furthermore, activated CD8-positive cells in response to MAC infection in these mice seemed to not be relevant in the control of MAC infection. |
| format |
article |
| author |
Masayuki Nakajima Masashi Matsuyama Mio Kawaguchi Sosuke Matsumura Takumi Kiwamoto Yosuke Matsuno Yuko Morishima Kazufumi Yoshida Mingma Thsering Sherpa Kai Yazaki Ryota Tanaka Naoko Okiyama Masafumi Muratani Yukio Ishii Nobuyuki Hizawa |
| author_facet |
Masayuki Nakajima Masashi Matsuyama Mio Kawaguchi Sosuke Matsumura Takumi Kiwamoto Yosuke Matsuno Yuko Morishima Kazufumi Yoshida Mingma Thsering Sherpa Kai Yazaki Ryota Tanaka Naoko Okiyama Masafumi Muratani Yukio Ishii Nobuyuki Hizawa |
| author_sort |
Masayuki Nakajima |
| title |
Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium |
| title_short |
Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium |
| title_full |
Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium |
| title_fullStr |
Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium |
| title_full_unstemmed |
Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium |
| title_sort |
depletion of pd-1 or pd-l1 did not affect the mortality of mice infected with mycobacterium avium |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/56971edd017d426bbeae3d06975f937a |
| work_keys_str_mv |
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1718381026746564608 |