Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice
ABSTRACT Mycoplasma pneumoniae (Mp) residing extracellularly in the respiratory tract is the primary cause of bacterial community-acquired pneumonia in humans. However, the detailed pathological mechanism of Mp infection, especially inflammation in the lung, remains unclear. This study examined the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2021-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01588-21 |
| _version_ | 1828126740115881984 |
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| author | Shigeyuki Tamiya Eisuke Yoshikawa Monami Ogura Etsushi Kuroda Koichiro Suzuki Yasuo Yoshioka |
| author_facet | Shigeyuki Tamiya Eisuke Yoshikawa Monami Ogura Etsushi Kuroda Koichiro Suzuki Yasuo Yoshioka |
| author_sort | Shigeyuki Tamiya |
| collection | DOAJ |
| description | ABSTRACT Mycoplasma pneumoniae (Mp) residing extracellularly in the respiratory tract is the primary cause of bacterial community-acquired pneumonia in humans. However, the detailed pathological mechanism of Mp infection, especially inflammation in the lung, remains unclear. This study examined the role of the neutrophils in the inflammation of Mp-induced pneumonia in mice and the mechanism of neutrophil infiltration into the lungs in the Mp-induced pneumonia. We observed massive infiltration of neutrophils in the bronchoalveolar lavage fluid (BALF) and lung injury after the Mp challenge. The neutrophils were shown to contribute to lung injury in Mp pneumonia but were not involved in eliminating Mp, suggesting that neutrophils are detrimental to the host in Mp pneumonia. Mp also induced the production of inflammatory cytokines and chemokines in the BALF in a toll-like receptor 2 (TLR2)-dependent manner. Particularly, both interleukin (IL)-1α and IL-12 p40 played a crucial role in neutrophil infiltration into the BALF in a coordinated manner. Both IL-1α and IL-12 p40 were released from the alveolar macrophages depending on the TLR2 and reactive oxygen species. In addition, the community-acquired respiratory distress syndrome (CARDS) toxin from Mp were found to induce neutrophil infiltration into BALF in a TLR2-independent and IL-1α-dependent manner. Collectively, the TLR2-dependent production of both IL-1α and IL-12 p40, and CARDS toxin have been elucidated to play an important role in neutrophil infiltration into the lungs subsequently leading to the lung injury upon Mp infection in mice. These data will aid in the development of therapeutics and vaccines for Mp pneumonia. IMPORTANCE Although Mp-induced pneumonia is usually a self-limiting disease, refractory life-threatening pneumonia is often induced. In addition, the development of alternative therapeutic strategies for Mp is expected because of the emergence of antibiotic-resistant Mp. However, the lack of knowledge regarding the pathogenesis of Mp-induced pneumonia, especially inflammation upon the Mp infection, makes it tedious to design novel therapeutics and vaccines. For example, although neutrophil infiltration is widely recognized as one of the characteristics of Mp-induced pneumonia, the precise role of neutrophils in the aggravation of Mp pneumonia remains unclear. This study showed that the infiltration of neutrophils in the lungs is detrimental to the host in Mp-induced pneumonia in mice. Furthermore, the TLR2-dependent IL-1α and IL-12 p40 production, and CARDS toxin play important roles in neutrophil infiltration into the lung, following lung injury. Our findings apply to the rational design of novel therapeutics and vaccines against Mp. |
| first_indexed | 2024-04-11T15:40:00Z |
| format | Article |
| id | doaj.art-21ae2f14cf224f4abcd9deeb882257cc |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-11T15:40:00Z |
| publishDate | 2021-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-21ae2f14cf224f4abcd9deeb882257cc2022-12-22T04:15:51ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972021-12-019310.1128/spectrum.01588-21Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in MiceShigeyuki Tamiya0Eisuke Yoshikawa1Monami Ogura2Etsushi Kuroda3Koichiro Suzuki4Yasuo Yoshioka5Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, JapanLaboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, JapanLaboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, JapanDepartment of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo, JapanThe Research Foundation for Microbial Diseases of Osaka University, Suita, Osaka, JapanLaboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, JapanABSTRACT Mycoplasma pneumoniae (Mp) residing extracellularly in the respiratory tract is the primary cause of bacterial community-acquired pneumonia in humans. However, the detailed pathological mechanism of Mp infection, especially inflammation in the lung, remains unclear. This study examined the role of the neutrophils in the inflammation of Mp-induced pneumonia in mice and the mechanism of neutrophil infiltration into the lungs in the Mp-induced pneumonia. We observed massive infiltration of neutrophils in the bronchoalveolar lavage fluid (BALF) and lung injury after the Mp challenge. The neutrophils were shown to contribute to lung injury in Mp pneumonia but were not involved in eliminating Mp, suggesting that neutrophils are detrimental to the host in Mp pneumonia. Mp also induced the production of inflammatory cytokines and chemokines in the BALF in a toll-like receptor 2 (TLR2)-dependent manner. Particularly, both interleukin (IL)-1α and IL-12 p40 played a crucial role in neutrophil infiltration into the BALF in a coordinated manner. Both IL-1α and IL-12 p40 were released from the alveolar macrophages depending on the TLR2 and reactive oxygen species. In addition, the community-acquired respiratory distress syndrome (CARDS) toxin from Mp were found to induce neutrophil infiltration into BALF in a TLR2-independent and IL-1α-dependent manner. Collectively, the TLR2-dependent production of both IL-1α and IL-12 p40, and CARDS toxin have been elucidated to play an important role in neutrophil infiltration into the lungs subsequently leading to the lung injury upon Mp infection in mice. These data will aid in the development of therapeutics and vaccines for Mp pneumonia. IMPORTANCE Although Mp-induced pneumonia is usually a self-limiting disease, refractory life-threatening pneumonia is often induced. In addition, the development of alternative therapeutic strategies for Mp is expected because of the emergence of antibiotic-resistant Mp. However, the lack of knowledge regarding the pathogenesis of Mp-induced pneumonia, especially inflammation upon the Mp infection, makes it tedious to design novel therapeutics and vaccines. For example, although neutrophil infiltration is widely recognized as one of the characteristics of Mp-induced pneumonia, the precise role of neutrophils in the aggravation of Mp pneumonia remains unclear. This study showed that the infiltration of neutrophils in the lungs is detrimental to the host in Mp-induced pneumonia in mice. Furthermore, the TLR2-dependent IL-1α and IL-12 p40 production, and CARDS toxin play important roles in neutrophil infiltration into the lung, following lung injury. Our findings apply to the rational design of novel therapeutics and vaccines against Mp.https://journals.asm.org/doi/10.1128/spectrum.01588-21alveolar macrophageinfectioninflammationlung injuryMycoplasma pneumoniaeneutrophils |
| spellingShingle | Shigeyuki Tamiya Eisuke Yoshikawa Monami Ogura Etsushi Kuroda Koichiro Suzuki Yasuo Yoshioka Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice Microbiology Spectrum alveolar macrophage infection inflammation lung injury Mycoplasma pneumoniae neutrophils |
| title | Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice |
| title_full | Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice |
| title_fullStr | Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice |
| title_full_unstemmed | Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice |
| title_short | Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice |
| title_sort | neutrophil mediated lung injury both via tlr2 dependent production of il 1α and il 12 p40 and tlr2 independent cards toxin after mycoplasma pneumoniae infection in mice |
| topic | alveolar macrophage infection inflammation lung injury Mycoplasma pneumoniae neutrophils |
| url | https://journals.asm.org/doi/10.1128/spectrum.01588-21 |
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