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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00399

Chlamydia trachomatis serovars drive differential production of proinflammatory cytokines and chemokines depending on the type of cell infected

 Robert Faris1,  Shelby Andersen1, Alix McCullough1, Francoise Gourronc1, Al Klingelhutz1 and  Mary M. Weber1*
  • 1The University of Iowa, United States

Chlamydia trachomatis serovars A-C infect conjunctival epithelial cells and untreated infection can lead to blindness. D-K infect genital tract epithelial cells resulting in pelvic inflammatory disease, ectopic pregnancy, and sterility while L1-L3 infect epithelial cells and macrophages, causing an invasive infection. Despite some strains of chlamydia sharing high nucleotide sequence similarity, the bacterial and host factors that govern tissue and cellular tropism remain largely unknown. Following introduction of C.trachomatis via intercourse, epithelial cells of the vagina, foreskin, and ectocervix are exposed to large numbers of the pathogen, yet their response to infection and the dynamics of chlamydial growth in these cells has not been well characterized compared to growth in more permissive cell types that harbor C.trachomatis. We compared intracellular replication and inclusion development of representative C.trachomatis serovars in immortalized human conjunctival epithelial, urogenital epithelial, PMA stimulated THP-1 (macrophages), and HeLa cells. We demonstrate that urogenital epithelial cells of the vagina, ectocervix, and foreskin restrict replication of serovar A while promoting robust replication and inclusion development of serovar D and L2. Macrophages restrict serovars D and A while L2 proliferates well in these cells. Furthermore, we show that GM-CSF, RANTES, GROα, IL-1α, IL-1β, IP-10, IL-8, and IL-18 are produced in a cell-type and serovar-specific manner. Collectively we have established a series of human cell lines that represent some of the first cell types to encounter C.trachomatis following exposure and show that differential production of key cytokines early during infection could regulate serovar-host cell specificity.

Keywords: Chlamydia trachomatis, innate immune response, Trachoma, Serovariants, chemokine, cytokine, macrophage

Received: 27 Aug 2019; Accepted: 07 Nov 2019.

Copyright: © 2019 Faris, Andersen, McCullough, Gourronc, Klingelhutz and Weber. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mary M. Weber, The University of Iowa, Iowa City, 52242, Iowa, United States, mary-weber@uiowa.edu