title: Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.
abstract: Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases.
authors.affiliation: Centre for Clinical Microbiology, Division of Infection and Immunity, University College London (UCL), London, UK; National Institute for Health Research Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Rao
authors.affiliation: Aurum Institute, Johannesburg, South Africa.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wallis
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: South African Medical Research Council, Cape Town, South Africa.
authors.forename: Roxana
authors.initials: R
authors.lastname: Rustomjee
authors.affiliation: University of Zambia-UCL Medical School (UNZA-UCLMS) Research and Training Project, University Teaching Hospital, Lusaka, Zambia; Ministry of Health, Lusaka, Zambia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mwaba
authors.affiliation: Unitat de Tuberculosi Experimental Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol CIBER Enfermedades Respiratorias, Can Ruti Campus, Edifici Laboratoris de Recerca, Barcelona, Spain.
authors.forename: Cris
authors.initials: C
authors.lastname: Vilaplana
authors.affiliation: Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Yeboah-Manu
authors.affiliation: Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Chakaya
authors.affiliation: National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.affiliation: Special Infectious Agents Unit, King Fahd Medical Research Centre, and Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Esam
authors.initials: E
authors.lastname: Azhar
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; DZIF German Centre for Infection Research, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003141:Communicable Diseases / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000627:therapeutic use; D004351:Drug Resistance; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D014815:Vitamins