Antibiotic treatment does not abrogate protection against Mycobacterium tuberculosis reinfection in Macaques

Abstract

AbstractConcomitant immunity is generally defined as an ongoing infection providing protection against reinfection1. Its role in prevention of tuberculosis (TB) caused byMycobacterium tuberculosis(Mtb) is supported by epidemiological evidence in humans as well as experimental evidence in mice and non-human primates (NHPs). Whether the presence of live Mtb, rather than simply persistent antigen, is necessary for concomitant immunity in TB is still unclear. Here, we investigated whether live Mtb plays a measurable role in control of secondary Mtb infection. Using cynomolgus macaques, molecularly barcoded Mtb libraries, PET-CT imaging, flow cytometry and cytokine profiling we evaluated the effect of antibiotic treatment after primary infection on immunological response and bacterial establishment, dissemination, and burden post-secondary infection. Our data provide evidence that, in this experimental model, treatment with antibiotics after primary infection reduced inflammation in the lung but was not associated with a significant change in bacterial establishment or burden in the lung or lymph nodes. Treatment of the primary infection also did not change the restriction on bacterial dissemination to other tissues, or growth of Mtb from the secondary infection in thoracic lymph nodes. These findings support that antibiotic-treated animals were still able to restrict bacterial establishment and dissemination, indicating that, at least in NHPs, antibiotic treatment does not substantially increase susceptibility to Mtb infection or TB disease upon secondary infection.