Modulation of Inflammation and Immune Responses by Heme Oxygenase-1: Implications for Infection with Intracellular Pathogens

Author(s)

Costa, Diego L. ^[1] ; Amaral, Eduardo P. ^[2] ; Andrade, Bruno B. ^{[3, 4, 5, 6, 7, 8, 9]} ; Sher, Alan ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] NIAID, Immunobiol Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 - USA

^[3] Fundacao Oswaldo Cruz, Inst Goncalo Moniz, BR-40296710 Salvador, BA - Brazil

^[4] Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, ZA-7925 Cape Town - South Africa

^[5] Multinatl Org Network Sponsoring Translat & Epide, BR-40210320 Salvador, BA - Brazil

^[6] Fac Tecnol & Ciencias UniFTC, Curso Med, BR-41741590 Salvador, BA - Brazil

^[7] Univ Salvador UNIFACS, Laureate Int Univ, Curso Med, BR-41770235 Salvador, BA - Brazil

^[8] Escola Bahiana Med & Saude Publ EBMSP, BR-40290000 Salvador, BA - Brazil

^[9] Vanderbilt Univ, Dept Med, Div Infect Dis, Sch Med, Nashville, TN 37232 - USA

• Document type: Review article
• Source: ANTIOXIDANTS; v. 9, n. 12 DEC 2020.
• Web of Science Citations: 0

Abstract

Heme oxygenase-1 (HO-1) catalyzes the degradation of heme molecules releasing equimolar amounts of biliverdin, iron and carbon monoxide. Its expression is induced in response to stress signals such as reactive oxygen species and inflammatory mediators with antioxidant, anti-inflammatory and immunosuppressive consequences for the host. Interestingly, several intracellular pathogens responsible for major human diseases have been shown to be powerful inducers of HO-1 expression in both host cells and in vivo. Studies have shown that this HO-1 response can be either host detrimental by impairing pathogen control or host beneficial by limiting infection induced inflammation and tissue pathology. These properties make HO-1 an attractive target for host-directed therapy (HDT) of the diseases in question, many of which have been difficult to control using conventional antibiotic approaches. Here we review the mechanisms by which HO-1 expression is induced and how the enzyme regulates inflammatory and immune responses during infection with a number of different intracellular bacterial and protozoan pathogens highlighting mechanistic commonalities and differences with the goal of identifying targets for disease intervention. (AU)

• FAPESP's process: 19/08445-8 - Immunomodulation of iron homeostasis and regulation of tyrosine kinase TAM receptor signaling pathway during Mycobacterium tuberculosis infection: targets for the development of host-directed immunopharmacological therapies
• Grantee: Diego Luís Costa
• Support Opportunities: Research Grants - Young Investigators Grants