NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection
Streptococcus pneumoniae is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies ha...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.898559/full |
| _version_ | 1818549923119890432 |
|---|---|
| author | Qi Tao Dongyi Xu Dongyi Xu Kaixiang Jia Xinrui Cao Chao Ye Sanlei Xie Dong-Liang Hu Lianci Peng Rendong Fang Rendong Fang |
| author_facet | Qi Tao Dongyi Xu Dongyi Xu Kaixiang Jia Xinrui Cao Chao Ye Sanlei Xie Dong-Liang Hu Lianci Peng Rendong Fang Rendong Fang |
| author_sort | Qi Tao |
| collection | DOAJ |
| description | Streptococcus pneumoniae is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies have shown that NLRP6 plays a negative regulatory role in host defense against S. pneumoniae, but the underlying mechanism is still unclear. The further negative regulatory role of NLRP6 in the host was investigated in this study. Our results showed that NLRP6−/− mice in the lung had lower bacterial burdens after S. pneumoniae infection and expressed higher level of tight junction (TJ) protein occludin compared to WT mice, indicating the detrimental role of NLRP6 in the host defense against S. pneumoniae infection. Transcriptome analysis showed that genes related to leukocytes migration and recruitment were differentially expressed between wild-type (WT) and NLRP6 knockout (NLRP6−/−) mice during S. pneumoniae infection. Also, NLRP6−/− mice showed higher expression of chemokines including C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) and lower gene expression of complement C3a receptor 1 (C3aR1) and P-selectin glycoprotein ligand-1 (PSGL-1) which are the factors that inhibit the recruitment of neutrophils. Furthermore, NLRP6−/− neutrophils showed increased intracellular bactericidal ability and the formation of neutrophil extracellular traps (NETs) during S. pneumoniae infection. Taken together, our study suggests that NLRP6 is a negative regulator of neutrophil recruitment and function during S. pneumoniae infection. Our study provides a new insight to develop novel strategies to treat invasive pneumococcal infection. |
| first_indexed | 2024-12-12T08:39:35Z |
| format | Article |
| id | doaj.art-4b0d4e5bcd0e4bd3a88c98b9984d0dcf |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T08:39:35Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-4b0d4e5bcd0e4bd3a88c98b9984d0dcf2022-12-22T00:30:49ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-05-011310.3389/fmicb.2022.898559898559NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae InfectionQi Tao0Dongyi Xu1Dongyi Xu2Kaixiang Jia3Xinrui Cao4Chao Ye5Sanlei Xie6Dong-Liang Hu7Lianci Peng8Rendong Fang9Rendong Fang10Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaDepartment of Medical Microbiology and Infection Prevention at University of Groningen/University Medical Center Groningen, Groningen, NetherlandsJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaDepartment of Zoonoses, Kitasato University School of Veterinary Medicine, Towada, JapanJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Herbivore Science, Chongqing, ChinaStreptococcus pneumoniae is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies have shown that NLRP6 plays a negative regulatory role in host defense against S. pneumoniae, but the underlying mechanism is still unclear. The further negative regulatory role of NLRP6 in the host was investigated in this study. Our results showed that NLRP6−/− mice in the lung had lower bacterial burdens after S. pneumoniae infection and expressed higher level of tight junction (TJ) protein occludin compared to WT mice, indicating the detrimental role of NLRP6 in the host defense against S. pneumoniae infection. Transcriptome analysis showed that genes related to leukocytes migration and recruitment were differentially expressed between wild-type (WT) and NLRP6 knockout (NLRP6−/−) mice during S. pneumoniae infection. Also, NLRP6−/− mice showed higher expression of chemokines including C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) and lower gene expression of complement C3a receptor 1 (C3aR1) and P-selectin glycoprotein ligand-1 (PSGL-1) which are the factors that inhibit the recruitment of neutrophils. Furthermore, NLRP6−/− neutrophils showed increased intracellular bactericidal ability and the formation of neutrophil extracellular traps (NETs) during S. pneumoniae infection. Taken together, our study suggests that NLRP6 is a negative regulator of neutrophil recruitment and function during S. pneumoniae infection. Our study provides a new insight to develop novel strategies to treat invasive pneumococcal infection.https://www.frontiersin.org/articles/10.3389/fmicb.2022.898559/fullStreptococcus pneumoniaeNLRP6neutrophilsneutrophil extracellular trapshost defense |
| spellingShingle | Qi Tao Dongyi Xu Dongyi Xu Kaixiang Jia Xinrui Cao Chao Ye Sanlei Xie Dong-Liang Hu Lianci Peng Rendong Fang Rendong Fang NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection Frontiers in Microbiology Streptococcus pneumoniae NLRP6 neutrophils neutrophil extracellular traps host defense |
| title | NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection |
| title_full | NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection |
| title_fullStr | NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection |
| title_full_unstemmed | NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection |
| title_short | NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection |
| title_sort | nlrp6 serves as a negative regulator of neutrophil recruitment and function during streptococcus pneumoniae infection |
| topic | Streptococcus pneumoniae NLRP6 neutrophils neutrophil extracellular traps host defense |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.898559/full |
| work_keys_str_mv | AT qitao nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT dongyixu nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT dongyixu nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT kaixiangjia nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT xinruicao nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT chaoye nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT sanleixie nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT donglianghu nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT liancipeng nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT rendongfang nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection AT rendongfang nlrp6servesasanegativeregulatorofneutrophilrecruitmentandfunctionduringstreptococcuspneumoniaeinfection |