Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection
Mycobacterium abscessus is a nontuberculous mycobacterium emerging as a significant pathogen in individuals with chronic lung diseases, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. Strategies of bacterial control based on host defenses...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1445660/full |
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| author | Emily A. Wheeler Patricia M. Lenhart-Pendergrass Noel M. Rysavy Katie R. Poch Silvia M. Caceres Kara M. Calhoun Karina A. Serban Karina A. Serban Jerry A. Nick Jerry A. Nick Kenneth C. Malcolm Kenneth C. Malcolm |
| author_facet | Emily A. Wheeler Patricia M. Lenhart-Pendergrass Noel M. Rysavy Katie R. Poch Silvia M. Caceres Kara M. Calhoun Karina A. Serban Karina A. Serban Jerry A. Nick Jerry A. Nick Kenneth C. Malcolm Kenneth C. Malcolm |
| author_sort | Emily A. Wheeler |
| collection | DOAJ |
| description | Mycobacterium abscessus is a nontuberculous mycobacterium emerging as a significant pathogen in individuals with chronic lung diseases, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. Strategies of bacterial control based on host defenses are appealing; however, antimycobacterial immunity remains poorly understood and is further complicated by the appearance of smooth and rough morphotypes, which elicit distinct host responses. We investigated the role of serum components in neutrophil-mediated clearance of M. abscessus morphotypes. M. abscessus opsonization with complement enhanced bacterial killing compared to complement-deficient opsonization. Killing of rough isolates was less reliant on complement. Complement C3 and mannose-binding lectin 2 (MBL2) were deposited on M. abscessus morphotypes in distinct patterns, with a greater association of MBL2 on rough M. abscessus. Killing was dependent on C3; however, depletion and competition experiments indicate that canonical complement activation pathways are not involved. Complement-mediated killing relied on natural IgG and IgM for smooth morphotypes and on IgG for rough morphotypes. Both morphotypes were recognized by complement receptor 3 in a carbohydrate- and calcium-dependent manner. These findings indicate a role for noncanonical C3 activation pathways for M. abscessus clearance by neutrophils and link smooth-to-rough adaptation to complement activation. |
| format | Article |
| id | doaj-art-9ffc1e1327434f9982a862a12873abae |
| institution | DOAJ |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-9ffc1e1327434f9982a862a12873abae2025-08-20T02:56:27ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-03-011510.3389/fcimb.2025.14456601445660Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infectionEmily A. Wheeler0Patricia M. Lenhart-Pendergrass1Noel M. Rysavy2Katie R. Poch3Silvia M. Caceres4Kara M. Calhoun5Karina A. Serban6Karina A. Serban7Jerry A. Nick8Jerry A. Nick9Kenneth C. Malcolm10Kenneth C. Malcolm11Department of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Pediatrics, University of Colorado, Aurora, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine University of Colorado, Aurora, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine University of Colorado, Aurora, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine University of Colorado, Aurora, CO, United StatesDepartment of Medicine, National Jewish Health, Denver, CO, United StatesDepartment of Medicine University of Colorado, Aurora, CO, United StatesMycobacterium abscessus is a nontuberculous mycobacterium emerging as a significant pathogen in individuals with chronic lung diseases, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. Strategies of bacterial control based on host defenses are appealing; however, antimycobacterial immunity remains poorly understood and is further complicated by the appearance of smooth and rough morphotypes, which elicit distinct host responses. We investigated the role of serum components in neutrophil-mediated clearance of M. abscessus morphotypes. M. abscessus opsonization with complement enhanced bacterial killing compared to complement-deficient opsonization. Killing of rough isolates was less reliant on complement. Complement C3 and mannose-binding lectin 2 (MBL2) were deposited on M. abscessus morphotypes in distinct patterns, with a greater association of MBL2 on rough M. abscessus. Killing was dependent on C3; however, depletion and competition experiments indicate that canonical complement activation pathways are not involved. Complement-mediated killing relied on natural IgG and IgM for smooth morphotypes and on IgG for rough morphotypes. Both morphotypes were recognized by complement receptor 3 in a carbohydrate- and calcium-dependent manner. These findings indicate a role for noncanonical C3 activation pathways for M. abscessus clearance by neutrophils and link smooth-to-rough adaptation to complement activation.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1445660/fullcystic fibrosisnatural antibodiescomplementneutrophilsadaptation |
| spellingShingle | Emily A. Wheeler Patricia M. Lenhart-Pendergrass Noel M. Rysavy Katie R. Poch Silvia M. Caceres Kara M. Calhoun Karina A. Serban Karina A. Serban Jerry A. Nick Jerry A. Nick Kenneth C. Malcolm Kenneth C. Malcolm Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection Frontiers in Cellular and Infection Microbiology cystic fibrosis natural antibodies complement neutrophils adaptation |
| title | Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection |
| title_full | Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection |
| title_fullStr | Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection |
| title_full_unstemmed | Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection |
| title_short | Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection |
| title_sort | divergent host humoral innate immune response to the smooth to rough adaptation of mycobacterium abscessus in chronic infection |
| topic | cystic fibrosis natural antibodies complement neutrophils adaptation |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1445660/full |
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