Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis.
Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication of M. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation.
Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
Alimuddin
A
Zumla
F79, Therapeutic Immunology (TIM) division, Department of Laboratory Medicine (LABMED), Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden.
Martin
M
Rao
F79, Therapeutic Immunology (TIM) division, Department of Laboratory Medicine (LABMED), Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden.
Ernest
E
Dodoo
F79, Therapeutic Immunology (TIM) division, Department of Laboratory Medicine (LABMED), Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden. markus.maeurer@ki.se.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden. markus.maeurer@ki.se.
Markus
M
Maeurer
D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000995:Antitubercular Agents; D007155:Immunologic Factors
Host-directed therapies; Immune response; Immunomodulatory agents; Inflammation; Multidrug resistance; Tuberculosis