Reduction of host cell mitochondrial activity as M. leprae’s strategy to evade host innate immunity

• Published in: Immunological reviews 2021-04, Vol.301 (1), p.193-208
• Main Authors: de Oliveira, Marcus Fernandes, Medeiros, Rychelle Clayde Affonso, Mietto, Bruno Siqueira, Calvo, Thyago Leal, Mendonça, Ana Paula Miranda, Rosa, Thabatta Leal Silveira Andrezo, da Silva, Débora Santos, do Carmo de Vasconcelos, Karina Girardi, Pereira, Antonio Marcos Rodrigues, de Macedo, Cristiana Santos, Pereira, Geraldo Moura Batista, de Berrêdo Pinho Moreira, Marcia, Pessolani, Maria Cristina Vidal, Moraes, Milton Ozório, Lara, Flavio Alves
• Format: Article
• Language: English
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12962

Leprosy is a much-feared incapacitating infectious disease caused by Mycobacterium leprae or M. lepromatosis , annually affecting roughly 200,000 people worldwide. During host-pathogen interaction, M. leprae subverts the immune response, leading to development of disease. Throughout the last few decades, the impact of energy metabolism on the control of intracellular pathogens and leukocytic differentiation has become more evident. Mitochondria play a key role in regulating newly-discovered immune signaling pathways by controlling redox metabolism and the flow of energy besides activating inflammasome, xenophagy, and apoptosis. Likewise, this organelle, whose origin is probably an alphaproteobacterium, directly controls the intracellular pathogens attempting to invade its niche, a feat conquered at the expense of billions of years of coevolution. In the present review, we discuss the role of reduced host cell mitochondrial activity during M. leprae infection and the consequential fates of M. leprae and host innate immunity. Conceivably, inhibition of mitochondrial energy metabolism emerges as an overlooked and novel mechanism developed by M. leprae to evade xenophagy and the host immune response.