TY - JOUR
T1 - Experimental evidence for limited in vivo virulence of Mycobacterium africanum
AU - Cá, Baltazar
AU - Fonseca, Kaori L
AU - Sousa, Jeremy
AU - Maceiras, Ana Raquel
AU - Machado, Diana
AU - Sanca, Lilica
AU - Rabna, Paulo
AU - Rodrigues, Pedro N S
AU - Viveiros, Miguel
AU - Saraiva, Margarida
N1 - Funding Information:
The authors thank the excellent support from the i3S scientific platforms, namely Animal Facility and Translational Cytometry. Funding. This work was supported by Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 ? Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through Funda??o para a Ci?ncia e a Tecnologia, Minist?rio da Ci?ncia, Tecnologia e Inova??o in the framework of the project ?Institute for Research and Innovation in Health Sciences? (POCI-01-0145-FEDER-007274), and by grants FCT ? Aga Khan Development Network (ref 333197025), POCI-01-0145-FEDER-028955 (to MS), PTDC/BIA-MIC/30692/2017, and UID/Multi/04413/2013 (to DM and MV). BC and KF were funded by FCT Ph.D. scholarships SFRH/BD/114403/2016 and SFRH/BD/114405/2016, respectively. The Gulbenkian Foundation is acknowledged for a field work research grant to BC, Bolsas de apoio ? investiga??o para estudantes de doutoramento dos PALOP, Ref. P-146397. DM and MS were supported by FCT through Estimulo Individual ao Emprego Cient?fico.
Publisher Copyright:
© Copyright © 2019 Cá, Fonseca, Sousa, Maceiras, Machado, Sanca, Rabna, Rodrigues, Viveiros and Saraiva.
PY - 2019
Y1 - 2019
N2 - Tuberculosis remains a public health problem and a main cause of death to humans. Both Mycobacterium tuberculosis and Mycobacterium africanum cause tuberculosis. In contrast to M. tuberculosis, which is geographically spread, M. africanum is restricted to West Africa. Differences have also been found in the growth rate and type of disease caused by M. africanum, globally suggesting an attenuation of this bacteria. In this study, we used the mouse model of infection to follow the dynamics of M. africanum infection in terms of bacterial burdens and tissue pathology, as well as the immune response triggered. Our findings support a lower virulence of M. africanum as compared to M. tuberculosis, including in mice lacking IFN-γ, a major protective cytokine in tuberculosis. Furthermore, the lung immune response triggered by M. africanum infection in wild-type animals was characterized by a discrete influx of leukocytes and a modest transcriptional upregulation of inflammatory mediators. Our findings contribute to elucidate the pathogenesis of M. africanum, supporting the hypothesis that this is an attenuated member of the tuberculosis-causing bacteria. Understanding the biology of M. africanum and how it interacts with the host to establish infection will have implications for our knowledge of TB and for the development of novel and better tools to control this devastating disease.
AB - Tuberculosis remains a public health problem and a main cause of death to humans. Both Mycobacterium tuberculosis and Mycobacterium africanum cause tuberculosis. In contrast to M. tuberculosis, which is geographically spread, M. africanum is restricted to West Africa. Differences have also been found in the growth rate and type of disease caused by M. africanum, globally suggesting an attenuation of this bacteria. In this study, we used the mouse model of infection to follow the dynamics of M. africanum infection in terms of bacterial burdens and tissue pathology, as well as the immune response triggered. Our findings support a lower virulence of M. africanum as compared to M. tuberculosis, including in mice lacking IFN-γ, a major protective cytokine in tuberculosis. Furthermore, the lung immune response triggered by M. africanum infection in wild-type animals was characterized by a discrete influx of leukocytes and a modest transcriptional upregulation of inflammatory mediators. Our findings contribute to elucidate the pathogenesis of M. africanum, supporting the hypothesis that this is an attenuated member of the tuberculosis-causing bacteria. Understanding the biology of M. africanum and how it interacts with the host to establish infection will have implications for our knowledge of TB and for the development of novel and better tools to control this devastating disease.
KW - Tuberculosis
KW - Mycobacterium africanum
KW - Immune response
KW - Cytokines
KW - Pathology
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2019.02102/full
U2 - 10.3389/fmicb.2019.02102
DO - 10.3389/fmicb.2019.02102
M3 - Article
C2 - 31552007
SN - 1664-302X
VL - 10
SP - 2102
EP - 2111
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 2102
ER -