Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent
Abstract The mechanisms through which cells of the host innate immune system distinguish commensal bacteria from pathogens are currently unclear. Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) expressed by host cells which recognize microbe-associated molecular patter...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-85347-7 |
| _version_ | 1818430851187212288 |
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| author | Sreeram Udayan Ludovica F. Buttó Valerio Rossini Janaki Velmurugan Maria Martinez-Lopez David Sancho Silvia Melgar Paul W. O’Toole Ken Nally |
| author_facet | Sreeram Udayan Ludovica F. Buttó Valerio Rossini Janaki Velmurugan Maria Martinez-Lopez David Sancho Silvia Melgar Paul W. O’Toole Ken Nally |
| author_sort | Sreeram Udayan |
| collection | DOAJ |
| description | Abstract The mechanisms through which cells of the host innate immune system distinguish commensal bacteria from pathogens are currently unclear. Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) expressed by host cells which recognize microbe-associated molecular patterns (MAMPs) common to both commensal and pathogenic bacteria. Of the different TLRs, TLR2/6 recognize bacterial lipopeptides and trigger cytokines responses, especially to Gram-positive and Gram-negative pathogens. We report here that TLR2 is dispensable for triggering macrophage cytokine responses to different strains of the Gram-positive commensal bacterial species Lactobacillus salivarius. The L. salivarius UCC118 strain strongly upregulated expression of the PRRs, Mincle (Clec4e), TLR1 and TLR2 in macrophages while downregulating other TLR pathways. Cytokine responses triggered by L. salivarius UCC118 were predominantly TLR2-independent but MyD88-dependent. However, macrophage cytokine responses triggered by another Gram-positive commensal bacteria, Bifidobacterium breve UCC2003 were predominantly TLR2-dependent. Thus, we report a differential requirement for TLR2-dependency in triggering macrophage cytokine responses to different commensal Gram-positive bacteria. Furthermore, TNF-α responses to the TLR2 ligand FSL-1 and L. salivarius UCC118 were partially Mincle-dependent suggesting that PRR pathways such as Mincle contribute to the recognition of MAMPs on distinct Gram-positive commensal bacteria. Ultimately, integration of signals from these different PRR pathways and other MyD88-dependent pathways may determine immune responses to commensal bacteria at the host-microbe interface. |
| first_indexed | 2024-12-14T15:39:58Z |
| format | Article |
| id | doaj.art-33a9a9dedae24ab39a40cf5078e3c771 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:39:58Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-33a9a9dedae24ab39a40cf5078e3c7712022-12-21T22:55:38ZengNature PortfolioScientific Reports2045-23222021-03-0111111610.1038/s41598-021-85347-7Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependentSreeram Udayan0Ludovica F. Buttó1Valerio Rossini2Janaki Velmurugan3Maria Martinez-Lopez4David Sancho5Silvia Melgar6Paul W. O’Toole7Ken Nally8APC Microbiome Ireland, University College CorkAPC Microbiome Ireland, University College CorkAPC Microbiome Ireland, University College CorkAPC Microbiome Ireland, University College CorkImmunobiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC)Immunobiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC)APC Microbiome Ireland, University College CorkAPC Microbiome Ireland, University College CorkAPC Microbiome Ireland, University College CorkAbstract The mechanisms through which cells of the host innate immune system distinguish commensal bacteria from pathogens are currently unclear. Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) expressed by host cells which recognize microbe-associated molecular patterns (MAMPs) common to both commensal and pathogenic bacteria. Of the different TLRs, TLR2/6 recognize bacterial lipopeptides and trigger cytokines responses, especially to Gram-positive and Gram-negative pathogens. We report here that TLR2 is dispensable for triggering macrophage cytokine responses to different strains of the Gram-positive commensal bacterial species Lactobacillus salivarius. The L. salivarius UCC118 strain strongly upregulated expression of the PRRs, Mincle (Clec4e), TLR1 and TLR2 in macrophages while downregulating other TLR pathways. Cytokine responses triggered by L. salivarius UCC118 were predominantly TLR2-independent but MyD88-dependent. However, macrophage cytokine responses triggered by another Gram-positive commensal bacteria, Bifidobacterium breve UCC2003 were predominantly TLR2-dependent. Thus, we report a differential requirement for TLR2-dependency in triggering macrophage cytokine responses to different commensal Gram-positive bacteria. Furthermore, TNF-α responses to the TLR2 ligand FSL-1 and L. salivarius UCC118 were partially Mincle-dependent suggesting that PRR pathways such as Mincle contribute to the recognition of MAMPs on distinct Gram-positive commensal bacteria. Ultimately, integration of signals from these different PRR pathways and other MyD88-dependent pathways may determine immune responses to commensal bacteria at the host-microbe interface.https://doi.org/10.1038/s41598-021-85347-7 |
| spellingShingle | Sreeram Udayan Ludovica F. Buttó Valerio Rossini Janaki Velmurugan Maria Martinez-Lopez David Sancho Silvia Melgar Paul W. O’Toole Ken Nally Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent Scientific Reports |
| title | Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent |
| title_full | Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent |
| title_fullStr | Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent |
| title_full_unstemmed | Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent |
| title_short | Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent |
| title_sort | macrophage cytokine responses to commensal gram positive lactobacillus salivarius strains are tlr2 independent and myd88 dependent |
| url | https://doi.org/10.1038/s41598-021-85347-7 |
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