{"doi":"10.1101/2022.05.01.490220","title":"Fc-engineered antibodies leverage neutrophils to drive control of <i>Mycobacterium tuberculosis</i>","abstract":"ABSTRACT Novel vaccination and therapeutic strategies are urgently needed to mitigate the tuberculosis (TB) epidemic. While extensive efforts have focused on potentiating cell-mediated immunity to control Mycobacterium tuberculosis ( Mtb ) infection, less effort has been invested in exploiting the humoral immune system to combat Mtb . Emerging data point to a role for antibodies in microbial control of Mtb , however the precise mechanism(s) of this control remain incompletely understood. Here we took an antibody Fc-engineering approach to determine whether Fc-modifications could improve the ability of antibodies to restrict Mtb , and to define Fc-mediated mechanism(s) antibodies leverage for this restriction. Using an antibody specific to the capsular polysaccharide α-glucan, we engineer a panel of Fc variants to augment or dampen select antibody effector functions, rationally building antibodies with enhanced capacity to promote Mtb restriction in a human whole blood model of infection. Surprisingly, restrictive Fc-engineered antibodies drive Mtb control in a neutrophil, not monocyte, dependent manner. Using single cell RNA sequencing, we show that restrictive antibodies promote neutrophil survival and expression of cell intrinsic antimicrobial programs. These data provide a roadmap for exploiting Fc-engineered antibodies as a novel class of TB therapeutics able to harness the protective functions of neutrophils to achieve disease control.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299178,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":91618,"name":"Joshua M. Peters","orcid":"0000-0001-9163-6706","position":1,"is_corresponding":false},{"id":652627,"name":"Richard Lu","orcid":null,"position":2,"is_corresponding":false},{"id":297928,"name":"Patricia S. Grace","orcid":"0000-0002-4604-0943","position":3,"is_corresponding":false},{"id":870426,"name":"Jaimie Sixsmith","orcid":null,"position":4,"is_corresponding":false},{"id":387485,"name":"Aaron S. Wallace","orcid":"0000-0003-2264-3229","position":5,"is_corresponding":false},{"id":988635,"name":"Matthew J. Schneider","orcid":"0000-0001-5667-4707","position":6,"is_corresponding":false},{"id":108386,"name":"Sally Shin","orcid":"0000-0002-9306-2264","position":7,"is_corresponding":false},{"id":989011,"name":"W Karpinski","orcid":null,"position":8,"is_corresponding":false},{"id":988636,"name":"Jeff C. Hsiao","orcid":"0000-0003-0800-9977","position":9,"is_corresponding":false},{"id":557641,"name":"Esther van Woudenbergh","orcid":"0000-0001-7363-6649","position":10,"is_corresponding":false},{"id":107237,"name":"Arturo Casadevall","orcid":"0000-0002-9402-9167","position":11,"is_corresponding":false},{"id":91622,"name":"Bryan D. Bryson","orcid":"0000-0003-1716-6712","position":12,"is_corresponding":false},{"id":249894,"name":"Lisa A. Cavacini","orcid":"0000-0003-1417-8339","position":13,"is_corresponding":false},{"id":106757,"name":"Galit Alter","orcid":"0000-0002-7680-9215","position":14,"is_corresponding":false},{"id":91624,"name":"Sarah M. Fortune","orcid":"0000-0001-7565-9975","position":15,"is_corresponding":false},{"id":260804,"name":"Edward B. Irvine","orcid":"0000-0002-8185-6454","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T00:31:40.528568Z","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":[]}