2016
DOI: 10.1073/pnas.1611987113
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Abstract: The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4 + T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivatio… Show more

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Cited by 114 publications
(201 citation statements)
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“…The Erdman strain has also been used in rhesus and cynomolgus macaques by other research groups (17)(18)(19)(20)(21), and a comparison of BCG vaccination followed by high-dose M. tuberculosis strain Erdman challenge in these two species suggested that cynomolgus macaques had improved control of infection (22). There is evidence for LTBI in rhesus macaques using the H37Rv strain delivered at a low dose (23) or the less virulent strain CDC1551 strain delivered at higher doses and reactivation of CDC1551 LTBI by SIV (24). The route of challenge (aerosol versus bronchoscopic challenge) in rhesus macaques influences the distribution of disease but not the overall outcome of the infection (25).…”
mentioning
confidence: 99%
“…The Erdman strain has also been used in rhesus and cynomolgus macaques by other research groups (17)(18)(19)(20)(21), and a comparison of BCG vaccination followed by high-dose M. tuberculosis strain Erdman challenge in these two species suggested that cynomolgus macaques had improved control of infection (22). There is evidence for LTBI in rhesus macaques using the H37Rv strain delivered at a low dose (23) or the less virulent strain CDC1551 strain delivered at higher doses and reactivation of CDC1551 LTBI by SIV (24). The route of challenge (aerosol versus bronchoscopic challenge) in rhesus macaques influences the distribution of disease but not the overall outcome of the infection (25).…”
mentioning
confidence: 99%
“…Immunostaining of lung sections from animals with asymptomatic LTBI showed that CXCR3+ CD4 T cells were present in lung tissue (Figure 8A) , with higher densities of CXCR3+ CD4 T cells in granulomatous areas of the lung compared to non-granulomatous areas ( Figure 8B ). Next, to investigate the relationship between lung CD4+CXCR3+ cells and Mtb burden, we stained archived lung tissue sections from rhesus macaques with active TB disease(24). Quantification of the density of CXCR3+CD4+ cells in the lungs of animals with active TB showed that the density of CXCR3+CD4+ cells was significantly (p=0.03) higher in the granulomatous areas compared to non-granulomatous areas of the lung, with overall lower CXCR3+CD4+ densities in the lungs of active TB relative to LTBI (Figure 8B) .…”
Section: Resultsmentioning
confidence: 99%
“…We have previously established a model of LTBI in Indian rhesus macaques, in which low-dose aerosol infection with Mtb CDC1551 leads to the development of asymptomatic Mtb infection. Approximately 80% of infected animals remained disease-free for up to 6 months post-infection (19-24) while only ∼20% progressed to active TB disease. In this study, we characterized the nature, magnitude and kinetics of Mtb antigen-specific CD4 and CD8 T cell responses during asymptomatic LTBI in rhesus macaques over the course of ∼24 weeks post-infection, by serially sampling blood and lung compartments in conjunction with intensive clinical monitoring.…”
Section: Introductionmentioning
confidence: 99%
“…The twenty adult rhesus macaques used in this study (Table S1 and S2) were bred and housed at the Tulane National Primate Research Center (TNPRC). All macaques were infected as previously described (Foreman et al, 2016;Mehra et al, 2011;Souriant et al, 2019). Briefly, aerosol infection was performed on macaques using a low dose (25 CFU implanted) of Mtb CDC1551.…”
Section: Non-human Primate (Nhp) Samplesmentioning
confidence: 99%