Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40
ABSTRACT Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus, group A and B streptococci, Escherichia coli, Neisseria gonorrho...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-04-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00106-22 |
| _version_ | 1818480153651576832 |
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| author | Patrick M. Schlievert Samuel H. Kilgore Andrea Benavides Aloysius J. Klingelhutz |
| author_facet | Patrick M. Schlievert Samuel H. Kilgore Andrea Benavides Aloysius J. Klingelhutz |
| author_sort | Patrick M. Schlievert |
| collection | DOAJ |
| description | ABSTRACT Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus, group A and B streptococci, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. We have previously shown that staphylococcal and streptococcal superantigens induce inflammatory chemokines from vaginal epithelial cells through the immune costimulatory molecule CD40 through use of a CRISPR cas9 knockout mutant and complemented epithelial cell line. In this study, we show that the potential vaginal pathogens S. aureus, group A and B streptococci, E. coli, an Enterococcus faecalis strain, and C. albicans in part use CD40 to stimulate interleukin-8 (IL-8) production from human vaginal epithelial cells. In contrast, N. gonorrhoeae does not appear to use CD40 to signal IL-8 production. Normal flora Lactobacillus crispatus and an Enterococcus faecalis strain that produces reutericyclin do not induce IL-8. These data indicate that many potential pathogens, but no normal commensals, induce IL-8 to help disrupt the human vaginal epithelial barrier through CD40, thus providing a potential therapeutic target for drug development. IMPORTANCE Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus, group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli, and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. In contrast, Neisseria gonorrhoeae does not use CD40 to stimulate interleukin-8. Normal flora lactobacilli and at least one E. faecalis strain do not induce interleukin-8. |
| first_indexed | 2024-12-10T11:19:32Z |
| format | Article |
| id | doaj.art-6121bd74d4ba47259a877f055eab2d0b |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-10T11:19:32Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-6121bd74d4ba47259a877f055eab2d0b2022-12-22T01:51:02ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-04-0110210.1128/spectrum.00106-22Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40Patrick M. Schlievert0Samuel H. Kilgore1Andrea Benavides2Aloysius J. Klingelhutz3Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAABSTRACT Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus, group A and B streptococci, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. We have previously shown that staphylococcal and streptococcal superantigens induce inflammatory chemokines from vaginal epithelial cells through the immune costimulatory molecule CD40 through use of a CRISPR cas9 knockout mutant and complemented epithelial cell line. In this study, we show that the potential vaginal pathogens S. aureus, group A and B streptococci, E. coli, an Enterococcus faecalis strain, and C. albicans in part use CD40 to stimulate interleukin-8 (IL-8) production from human vaginal epithelial cells. In contrast, N. gonorrhoeae does not appear to use CD40 to signal IL-8 production. Normal flora Lactobacillus crispatus and an Enterococcus faecalis strain that produces reutericyclin do not induce IL-8. These data indicate that many potential pathogens, but no normal commensals, induce IL-8 to help disrupt the human vaginal epithelial barrier through CD40, thus providing a potential therapeutic target for drug development. IMPORTANCE Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus, group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli, and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. In contrast, Neisseria gonorrhoeae does not use CD40 to stimulate interleukin-8. Normal flora lactobacilli and at least one E. faecalis strain do not induce interleukin-8.https://journals.asm.org/doi/10.1128/spectrum.00106-22CD40CandidaEscherichia coliNeisseria gonorrhoeaeStaphylococcusStreptococcus |
| spellingShingle | Patrick M. Schlievert Samuel H. Kilgore Andrea Benavides Aloysius J. Klingelhutz Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40 Microbiology Spectrum CD40 Candida Escherichia coli Neisseria gonorrhoeae Staphylococcus Streptococcus |
| title | Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40 |
| title_full | Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40 |
| title_fullStr | Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40 |
| title_full_unstemmed | Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40 |
| title_short | Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40 |
| title_sort | pathogen stimulation of interleukin 8 from human vaginal epithelial cells through cd40 |
| topic | CD40 Candida Escherichia coli Neisseria gonorrhoeae Staphylococcus Streptococcus |
| url | https://journals.asm.org/doi/10.1128/spectrum.00106-22 |
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