Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection
Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previous...
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my.um.eprints.386152024-08-30T04:10:55Z http://eprints.um.edu.my/38615/ Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection Chan, Yee Teng Cheok, Yi Ying Cheong, Heng Choon Tan, Grace Min Yi Seow, Shi Rui Tang, Ting Fang Sulaiman, Sofiah Looi, Chung Yeng Gupta, Rishein Arulanandam, Bernard Wong, Won Fen R Medicine RA Public aspects of medicine Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a C. trachomatis infection model. C57BL/6 mice infected with the mouse pathogen Chlamydia muridarum were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b(+)CD11c(-)F4/80(+)) versus inflammatory macrophages (CD11b(+)CD11c(+)F4/80(+)), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in C. trachomatis infection. Our findings demonstrated an increased CD11b(+) cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of C. muridarum-infected mice. Furthermore, analysis of the C. trachomatis-infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an in vitro infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward C. trachomatis-infected HeLa 229 cells. Lastly, using immunoprecipitation-mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin. Australasian Society for Immunology (ASI) 2023-04 Article PeerReviewed Chan, Yee Teng and Cheok, Yi Ying and Cheong, Heng Choon and Tan, Grace Min Yi and Seow, Shi Rui and Tang, Ting Fang and Sulaiman, Sofiah and Looi, Chung Yeng and Gupta, Rishein and Arulanandam, Bernard and Wong, Won Fen (2023) Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection. Immunology and Cell Biology, 101 (4). pp. 305-320. ISSN 0818-9641, DOI https://doi.org/10.1111/imcb.12621 <https://doi.org/10.1111/imcb.12621>. 10.1111/imcb.12621 |
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R Medicine RA Public aspects of medicine Chan, Yee Teng Cheok, Yi Ying Cheong, Heng Choon Tan, Grace Min Yi Seow, Shi Rui Tang, Ting Fang Sulaiman, Sofiah Looi, Chung Yeng Gupta, Rishein Arulanandam, Bernard Wong, Won Fen Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection |
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Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a C. trachomatis infection model. C57BL/6 mice infected with the mouse pathogen Chlamydia muridarum were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b(+)CD11c(-)F4/80(+)) versus inflammatory macrophages (CD11b(+)CD11c(+)F4/80(+)), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in C. trachomatis infection. Our findings demonstrated an increased CD11b(+) cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of C. muridarum-infected mice. Furthermore, analysis of the C. trachomatis-infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an in vitro infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward C. trachomatis-infected HeLa 229 cells. Lastly, using immunoprecipitation-mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin. |
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Article |
author |
Chan, Yee Teng Cheok, Yi Ying Cheong, Heng Choon Tan, Grace Min Yi Seow, Shi Rui Tang, Ting Fang Sulaiman, Sofiah Looi, Chung Yeng Gupta, Rishein Arulanandam, Bernard Wong, Won Fen |
author_facet |
Chan, Yee Teng Cheok, Yi Ying Cheong, Heng Choon Tan, Grace Min Yi Seow, Shi Rui Tang, Ting Fang Sulaiman, Sofiah Looi, Chung Yeng Gupta, Rishein Arulanandam, Bernard Wong, Won Fen |
author_sort |
Chan, Yee Teng |
title |
Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection |
title_short |
Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection |
title_full |
Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection |
title_fullStr |
Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection |
title_full_unstemmed |
Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection |
title_sort |
influx of podoplanin-expressing inflammatory macrophages into the genital tract following chlamydia infection |
publisher |
Australasian Society for Immunology (ASI) |
publishDate |
2023 |
url |
http://eprints.um.edu.my/38615/ |
_version_ |
1811682081273544704 |