Early Clearance of Mycobacterium tuberculosis Is Associated With Increased Innate Immune Responses
AJ Verrall, M Schneider, B Alisjahbana… - The Journal of …, 2020 - academic.oup.com
The Journal of infectious diseases, 2020•academic.oup.com
Background A proportion of tuberculosis (TB) case contacts do not become infected, even
when heavily exposed. We studied the innate immune responses of TB case contacts to
understand their role in protection against infection with Mycobacterium tuberculosis, termed
“early clearance.” Methods Indonesian household contacts of TB cases were tested for
interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post
recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were …
when heavily exposed. We studied the innate immune responses of TB case contacts to
understand their role in protection against infection with Mycobacterium tuberculosis, termed
“early clearance.” Methods Indonesian household contacts of TB cases were tested for
interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post
recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were …
Background
A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed “early clearance.”
Methods
Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive.
Results
Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae.
Conclusions
Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.
Oxford University Press