{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:08:57Z","timestamp":1768504137051,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,18]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                  is a nontuberculous mycobacterium emerging as a significant pathogen for individuals with chronic lung disease, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. New strategies of bacterial control based on host defenses are appealing, but anti-mycobacterial immune mechanisms are poorly understood and are complicated by the appearance of smooth and rough morphotypes with distinct host responses. We explored the role of the complement system in the clearance of\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  morphotypes by neutrophils, an abundant cell in these infections.\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  opsonized with plasma from healthy individuals promoted greater killing by neutrophils compared to opsonization in heat-inactivated plasma. Rough clinical isolates were more resistant to complement but were still efficiently killed. Complement C3 associated strongly with the smooth morphotype while mannose-binding lectin 2 was associated with the rough morphotype. M. abscessus killing was dependent on C3, but not on C1q or Factor B; furthermore, competition of mannose-binding lectin 2 binding with mannan or N-acetyl-glucosamine during opsonization did not inhibit killing. These data suggest that\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  does not canonically activate complement through the classical, alternative, or lectin pathways. Complement-mediated killing was dependent on IgG and IgM for smooth and on IgG for rough\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  . Both morphotypes were recognized by Complement Receptor 3 (CD11b), but not CR1 (CD35), and in a carbohydrate- and calcium-dependent manner. These data suggest the smooth-to-rough adaptation changes complement recognition of\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  and that complement is an important factor for\n                  <jats:italic>M. abscessus<\/jats:italic>\n                  infection.\n                <\/jats:p>","DOI":"10.1101\/2023.05.15.540822","type":"posted-content","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T07:10:10Z","timestamp":1684393810000},"source":"Crossref","is-referenced-by-count":0,"title":["Divergent host innate immune response to the smooth-to-rough\n                  <i>M. abscessus<\/i>\n                  adaptation to chronic infection"],"prefix":"10.64898","author":[{"given":"Emily A","family":"Wheeler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-6642","authenticated-orcid":false,"given":"Patricia M.","family":"Lenhart-Pendergrass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel M.","family":"Rysavy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Poch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1827-5132","authenticated-orcid":false,"given":"Silvia","family":"Caceres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9815-5331","authenticated-orcid":false,"given":"Kara M.","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-3034","authenticated-orcid":false,"given":"Karina","family":"Serban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-3449","authenticated-orcid":false,"given":"Jerry A.","family":"Nick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8097-6059","authenticated-orcid":false,"given":"Kenneth C.","family":"Malcolm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023052006000809000_2023.05.15.540822v1.1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1097\/MCP.0000000000000816","article-title":"Nontuberculous mycobacteria in cystic fibrosis","volume":"27","year":"2021","journal-title":"Curr Opin Pulm Med"},{"key":"2023052006000809000_2023.05.15.540822v1.2","doi-asserted-by":"crossref","first-page":"659997","DOI":"10.3389\/fcimb.2021.659997","article-title":"Mycobacterium abscessus complex: A Review of Recent Developments in an Emerging Pathogen","volume":"11","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2023052006000809000_2023.05.15.540822v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000905"},{"key":"2023052006000809000_2023.05.15.540822v1.4","first-page":"36","article-title":"Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis","volume":"11","year":"2013","journal-title":"Ann Am Thorac Soc"},{"key":"2023052006000809000_2023.05.15.540822v1.5","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.cell.2022.04.024","article-title":"Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2023052006000809000_2023.05.15.540822v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1125"},{"key":"2023052006000809000_2023.05.15.540822v1.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8156"},{"key":"2023052006000809000_2023.05.15.540822v1.8","doi-asserted-by":"crossref","unstructured":"Honda JR , Virdi R , Chan ED. 2018. 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