{"doi":"10.4049/jimmunol.2000256","title":"Mannose-Binding Lectin Possesses Agglutination Activity and Promotes Opsonophagocytosis of Macrophages with Calreticulin Interaction in an Early Vertebrate","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The innate immune system is an ancient defense system in the process of biological evolution, which can quickly and efficiently resist pathogen infection. In mammals, mannose-binding lectin (MBL) is a key molecule in the innate immune and plays an essential role in the first line of host defense against pathogenic bacteria. However, the evolutionary origins and ancient roles of immune defense of MBL and its mechanism in clearance of microbial pathogens are still unclear, especially in early vertebrates. In this study, Oreochromis niloticus MBL (OnMBL) was successfully isolated and purified from the serum of Nile tilapia (O. niloticus). The OnMBL was able to bind and agglutinate with two important pathogens of tilapia, Streptococcus agalactiae and Aeromonas hydrophila. Interestingly, the OnMBL was able to significantly inhibit the proliferation of pathogenic bacteria and reduce the inflammatory response. Upon bacterial challenge, the downregulation of OnMBL expression by RNA interference could lead to rapid proliferation of the pathogenic bacteria, ultimately resulting in tilapia death. However, the phenotype was rescued by reinjection of the OnMBL, which restored the healthy status of the knockdown tilapia. Moreover, a mechanistic analysis revealed that the OnMBL could clear pathogenic bacteria by collaborating with cell-surface calreticulin to facilitate phagocytosis in a complement activation-independent manner. To our knowledge, these results provide the first evidence on the antibacterial response mechanism of MBL performing evolutionary conserved function to promote opsonophagocytosis of macrophages in early vertebrates and reveals new insights into the understanding of the evolutionary origins and ancient roles basis of the C-type lectins in the innate immune defense.</jats:p>","journal":"The Journal of Immunology","year":2020,"id":677801,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1650281,"name":"Xiaoxue Yin","orcid":null,"position":1,"is_corresponding":false},{"id":1770975,"name":"Hairong Wu","orcid":"0000-0002-0986-0061","position":2,"is_corresponding":false},{"id":236222,"name":"Yang Lei","orcid":"0000-0002-3572-0345","position":3,"is_corresponding":false},{"id":1770977,"name":"Kailiang Han","orcid":null,"position":4,"is_corresponding":false},{"id":1770978,"name":"Jinfeng Mo","orcid":null,"position":5,"is_corresponding":false},{"id":1254974,"name":"Zheng Guo","orcid":"0000-0003-2105-4537","position":6,"is_corresponding":false},{"id":236112,"name":"Jun Li","orcid":"0000-0002-5190-0733","position":7,"is_corresponding":false},{"id":1769143,"name":"Jianmin Ye","orcid":null,"position":8,"is_corresponding":false},{"id":1769141,"name":"Liangliang Mu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mannose-Binding Lectin Possesses Agglutination Activity and Promotes Opsonophagocytosis of Macrophages with Calreticulin Interaction in an Early Vertebrate","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The innate immune system is an ancient defense system in the process of biological evolution, which can quickly and efficiently resist pathogen infection. In mammals, mannose-binding lectin (MBL) is a key molecule in the innate immune and plays an essential role in the first line of host defense against pathogenic bacteria. However, the evolutionary origins and ancient roles of immune defense of MBL and its mechanism in clearance of microbial pathogens are still unclear, especially in early vertebrates. In this study, Oreochromis niloticus MBL (OnMBL) was successfully isolated and purified from the serum of Nile tilapia (O. niloticus). The OnMBL was able to bind and agglutinate with two important pathogens of tilapia, Streptococcus agalactiae and Aeromonas hydrophila. Interestingly, the OnMBL was able to significantly inhibit the proliferation of pathogenic bacteria and reduce the inflammatory response. Upon bacterial challenge, the downregulation of OnMBL expression by RNA interference could lead to rapid proliferation of the pathogenic bacteria, ultimately resulting in tilapia death. However, the phenotype was rescued by reinjection of the OnMBL, which restored the healthy status of the knockdown tilapia. Moreover, a mechanistic analysis revealed that the OnMBL could clear pathogenic bacteria by collaborating with cell-surface calreticulin to facilitate phagocytosis in a complement activation-independent manner. To our knowledge, these results provide the first evidence on the antibacterial response mechanism of MBL performing evolutionary conserved function to promote opsonophagocytosis of macrophages in early vertebrates and reveals new insights into the understanding of the evolutionary origins and ancient roles basis of the C-type lectins in the innate immune defense.</jats:p>","is_dataset_classified":null,"base_score":3.713572066704308,"endowment":3.713572066704308,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33199536","pmcid":null,"openalex_id":"https://openalex.org/W3101457359","authors":[],"funders":[{"funder_name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","grant_id":"31902396","title":null},{"funder_name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","grant_id":"31972818","title":null},{"funder_name":"Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation), China","grant_id":"2019A1515012065","title":null}],"total_grants":3,"fwci":1.2891,"citation_percentile":0.80537751,"influential_citations":0,"citation_trend":[{"year":2021,"count":4},{"year":2022,"count":6},{"year":2023,"count":8},{"year":2024,"count":10},{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://www.jimmunol.org/content/jimmunol/205/12/3443.full.pdf","host_type":"journal"},{"url":"https://www.jimmunol.org/content/jimmunol/205/12/3443.full.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/205/12/3443/61879230/ji2000256.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.2000256","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33199536","host_type":"repository"}],"fields_of_study":["Complement system in diseases","Aquaculture disease management and microbiota","Immune Cell Function and Interaction","Aeromonas hydrophila","Animals","Cichlids","Female","Fish Diseases","Fish Proteins","Gram-Negative Bacterial Infections","Mannose-Binding Lectin","Mice","Mice, Inbred BALB C","Streptococcal Infections","Streptococcus agalactiae"],"mesh_terms":["Animals","Female","Fish Diseases","Mice, Inbred BALB C","Streptococcal Infections","Streptococcus agalactiae","Gram-Negative Bacterial Infections","Aeromonas hydrophila","Cichlids","Fish Proteins","Mannose-Binding Lectin","Mice"],"keywords":["Biology","Mannan-binding lectin","Microbiology","Innate immune system","Pathogenic bacteria","Immune system","Complement system","C-type lectin","Lectin","Bacteria","Immunology","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T04:33:47.676467Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}