{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:04:39Z","timestamp":1785528279392,"version":"3.56.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Mycobacterium abscessus<\/jats:italic> 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 <jats:italic>M. abscessus<\/jats:italic> morphotypes. <jats:italic>M. abscessus<\/jats:italic> 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 <jats:italic>M. abscessus<\/jats:italic> morphotypes in distinct patterns, with a greater association of MBL2 on rough <jats:italic>M. abscessus<\/jats:italic>. 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 <jats:italic>M. abscessus<\/jats:italic> clearance by neutrophils and link smooth-to-rough adaptation to complement activation.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1445660","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T07:01:54Z","timestamp":1742281314000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Divergent host humoral innate immune response to the smooth-to-rough adaptation of Mycobacterium abscessus in chronic infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Emily A.","family":"Wheeler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"Lenhart-Pendergrass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel M.","family":"Rysavy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie R.","family":"Poch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia M.","family":"Caceres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara M.","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina A.","family":"Serban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry A.","family":"Nick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth C.","family":"Malcolm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.mib.2021.01.012","article-title":"Synthesis and recycling of the mycobacterial cell envelope","volume":"60","author":"Abrahams","year":"2021","journal-title":"Curr. Opin. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"E943","DOI":"10.1073\/pnas.1321390111","article-title":"Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation","volume":"111","author":"Bernut","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1007\/BF01646932","article-title":"The role of staphylococcal lectins in human granulocyte stimulation","volume":"16","author":"Beuth","year":"1988","journal-title":"Infection."},{"key":"B4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/0005-2736(74)90153-9","article-title":"Interaction between erythrocyte membrane proteins and complement components. II. The identification and peptide composition of complement components C3 and C4 desorbed from erythrocyte membranes","volume":"373","author":"Bhakdi","year":"1974","journal-title":"Biochim. Biophys. Acta"},{"key":"B5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1128\/CVI.00607-13","article-title":"Blood collection tubes influence serum ficolin-1 and ficolin-2 levels","volume":"21","author":"Brady","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1126\/science.aaf8156","article-title":"Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium","volume":"354","author":"Bryant","year":"2016","journal-title":"Science."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4700","DOI":"10.1128\/IAI.67.9.4700-4707.1999","article-title":"Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection","volume":"67","author":"Byrd","year":"1999","journal-title":"Infect. Immun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1128\/JCM.01478-08","article-title":"Acute respiratory failure involving an R variant of Mycobacterium abscessus","volume":"47","author":"Catherinot","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2756","DOI":"10.1021\/acsinfecdis.0c00490","article-title":"O-methylation of the glycopeptidolipid acyl chain defines surface hydrophobicity of mycobacterium abscessus and macrophage invasion","volume":"6","author":"Daher","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1093\/cid\/ciaa1125","article-title":"Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS\/ERS\/ESCMID\/IDSA clinical practice guideline","volume":"71","author":"Daley","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1513\/AnnalsATS.202009-1214OC","article-title":"Population genomics of mycobacterium abscessus from U.S. Cystic fibrosis care centers","volume":"18","author":"Davidson","year":"2021","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B12","doi-asserted-by":"publisher","first-page":"E10147","DOI":"10.1073\/pnas.1812984115","article-title":"MmpL8(MAB) controls Mycobacterium abscessus virulence and production of a previously unknown glycolipid family","volume":"115","author":"Dubois","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B13","doi-asserted-by":"publisher","first-page":"7100","DOI":"10.4049\/jimmunol.181.10.7100","article-title":"Aspergillus conidia activate the complement by the mannan-binding lectin C2 bypass mechanism","volume":"181","author":"Dumestre-Perard","year":"2008","journal-title":"J. Immunol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MCHD-0034-2016","article-title":"Complement receptors in myeloid cell adhesion and phagocytosis","volume":"4","author":"Dustin","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1136\/thx.2008.100073","article-title":"Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanism","volume":"64","author":"Fidler","year":"2009","journal-title":"Thorax."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.4049\/jimmunol.157.3.1184","article-title":"Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors","volume":"157","author":"Galon","year":"1996","journal-title":"J. Immunol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01750","article-title":"Regulation of the complement system by pentraxins","volume":"10","author":"Haapasalo","year":"2019","journal-title":"Front. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1189\/jlb.69.3.397","article-title":"Phagocytosis and killing of Mycobacterium avium complex by human neutrophils","volume":"69","author":"Hartmann","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157865","article-title":"Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection","volume":"7","author":"Hayes","year":"2022","journal-title":"JCI Insight"},{"key":"B20","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1093\/infdis\/jiad007","article-title":"A rough colony morphology of mycobacterium abscessus is associated with cavitary pulmonary disease and poor clinical outcome","volume":"227","author":"Hedin","year":"2023","journal-title":"J. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02029","article-title":"Global environmental nontuberculous mycobacteria and their contemporaneous man-made and natural niches","volume":"9","author":"Honda","year":"2018","journal-title":"Front. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1099\/mic.0.28625-0","article-title":"Spontaneous reversion of Mycobacterium abscessus from a smooth to a rough morphotype is associated with reduced expression of glycopeptidolipid and reacquisition of an invasive phenotype","volume":"152","author":"Howard","year":"2006","journal-title":"Microbiology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1600-065X.2009.0078.x","article-title":"Mannose-binding lectin and innate immunity","volume":"230","author":"Ip","year":"2009","journal-title":"Immunol. Rev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1182\/blood-2018-03-834598","article-title":"Polyreactive IgM initiates complement activation by PF4\/heparin complexes through the classical pathway","volume":"132","author":"Khandelwal","year":"2018","journal-title":"Blood."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx107","article-title":"Clinical Mycobacterium abscessus strain inhibits autophagy flux and promotes its growth in murine macrophages","volume":"75","author":"Kim","year":"2017","journal-title":"Pathog. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3762\/bjoc.15.1","article-title":"Lectins of Mycobacterium tuberculosis - rarely studied proteins","volume":"15","author":"Kolbe","year":"2019","journal-title":"Beilstein J. Org Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1084\/jem.169.5.1733","article-title":"The human mannose-binding protein functions as an opsonin","volume":"169","author":"Kuhlman","year":"1989","journal-title":"J. Exp. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"6445","DOI":"10.4049\/jimmunol.1002948","article-title":"Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion","volume":"186","author":"Laarman","year":"2011","journal-title":"J. Immunol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03279-22","article-title":"Deficient complement opsonization impairs mycobacterium avium killing by neutrophils in cystic fibrosis","volume":"11","author":"Lenhart-Pendergrass","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B30","first-page":"191","article-title":"Naturally occurring anti-band 3 antibodies have a unique affinity for C3","volume":"80","author":"Lutz","year":"1993","journal-title":"Immunology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-1-4939-8570-8_12","article-title":"Measuring neutrophil bactericidal activity","volume":"1809","author":"Malcolm","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196120","article-title":"Neutrophil killing of Mycobacterium abscessus by intra- and extracellular mechanisms","volume":"13","author":"Malcolm","year":"2018","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057402","article-title":"Mycobacterium abscessus induces a limited pattern of neutrophil activation that promotes pathogen survival","volume":"8","author":"Malcolm","year":"2013","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01874-22","article-title":"Specificity of immunoglobulin response to nontuberculous mycobacteria infection in people with cystic fibrosis","volume":"10","author":"Malcolm","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1513\/AnnalsATS.201309-310OC","article-title":"Clinical significance of a first positive nontuberculous mycobacteria culture in cystic fibrosis","volume":"11","author":"Martiniano","year":"2013","journal-title":"Ann. Am. Thorac. Soc"},{"key":"B36","doi-asserted-by":"publisher","first-page":"ra101","DOI":"10.1126\/scisignal.aaf1585","article-title":"Lipoarabinomannan binding to lactosylceramide in lipid rafts is essential for the phagocytosis of mycobacteria by human neutrophils","volume":"9","author":"Nakayama","year":"2016","journal-title":"Sci. Signal"},{"key":"B37","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1128\/IAI.68.2.688-693.2000","article-title":"Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition","volume":"68","author":"Neth","year":"2000","journal-title":"Infect. Immun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1097\/MCP.0000000000000816","article-title":"Nontuberculous mycobacteria in cystic fibrosis","volume":"27","author":"Nick","year":"2021","journal-title":"Curr. Opin. Pulm Med."},{"key":"B39","doi-asserted-by":"publisher","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","author":"Nick","year":"2022","journal-title":"Cell."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1021\/acsinfecdis.0c00361","article-title":"Polysaccharide succinylation enhances the intracellular survival of mycobacterium abscessus","volume":"6","author":"Palcekova","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00024-20","article-title":"Mycobacterium abscessus clearance by neutrophils is independent of autophagy","volume":"88","author":"Pohl","year":"2020","journal-title":"Infect. Immun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1086\/jid.1997.175.issue-5","article-title":"Interaction of human mannose-binding protein with Mycobacterium avium","volume":"175","author":"Polotsky","year":"1997","journal-title":"J. Infect. Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.4049\/jimmunol.0802181","article-title":"Mycobacterium abscessus Glycopeptidolipids mask underlying cell wall phosphatidyl-myo-inositol mannosides blocking induction of human macrophage TNF-alpha by preventing interaction with TLR2","volume":"183","author":"Rhoades","year":"2009","journal-title":"J. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"5898","DOI":"10.1128\/IAI.00014-07","article-title":"Importance of T cells, gamma interferon, and tumor necrosis factor in immune control of the rapid grower Mycobacterium abscessus in C57BL\/6 mice","volume":"75","author":"Rottman","year":"2007","journal-title":"Infect. Immun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/j.1462-5822.2010.01565.x","article-title":"Overexpression of proinflammatory TLR-2-signalling lipoproteins in hypervirulent mycobacterial variants","volume":"13","author":"Roux","year":"2011","journal-title":"Cell Microbiol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.160185","article-title":"The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages","volume":"6","author":"Roux","year":"2016","journal-title":"Open Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1128\/JCM.39.2.816-819.2001","article-title":"Fatal pulmonary infection due to multidrug-resistant Mycobacterium abscessus in a patient with cystic fibrosis","volume":"39","author":"Sanguinetti","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/infdis\/140.5.698","article-title":"The role of natural IgG and complement in the phagocytosis of type 4 Neisseria gonorrhoeae by human polymorphonuclear leukocytes","volume":"140","author":"Schiller","year":"1979","journal-title":"J. Infect. Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.4049\/jimmunol.1200816","article-title":"Natural IgM mediates complement-dependent uptake of Francisella tularensis by human neutrophils via complement receptors 1 and 3 in nonimmune serum","volume":"189","author":"Schwartz","year":"2012","journal-title":"J.\u00a0Immunol."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000905","article-title":"Skin and soft tissue infections due to rapidly growing mycobacteria","volume":"36","author":"Sepulcri","year":"2023","journal-title":"Curr. Opin. Infect. Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/978-981-15-1580-4_3","article-title":"CLEC5A: A promiscuous pattern recognition receptor to microbes and beyond","volume":"1204","author":"Sung","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"10680","DOI":"10.1073\/pnas.91.22.10680","article-title":"Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b\/CD18)","volume":"91","author":"Ueda","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.659997","article-title":"Mycobacterium abscessus complex: A Review of Recent Developments in an Emerging Pathogen","volume":"11","author":"Victoria","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023637","article-title":"Neutrophil extracellular trap (NET)-mediated killing of Pseudomonas aeruginosa: evidence of acquired resistance within the CF airway, independent of CFTR","volume":"6","author":"Young","year":"2011","journal-title":"PloS One"},{"key":"B55","doi-asserted-by":"publisher","first-page":"8071","DOI":"10.1074\/jbc.M111.301044","article-title":"Studies of the pattern recognition molecule H-ficolin: specificity and purification","volume":"287","author":"Zacho","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.4049\/jimmunol.150.7.3030","article-title":"Cocapping of the leukoadhesin molecules complement receptor type 3 and lymphocyte function-associated antigen-1 with Fc gamma receptor III on human neutrophils. Possible role of lectin-like interactions","volume":"150","author":"Zhou","year":"1993","journal-title":"J. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1445660\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T07:01:58Z","timestamp":1742281318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1445660\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":56,"alternative-id":["10.3389\/fcimb.2025.1445660"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1445660","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]},"article-number":"1445660"}}