Background and Objective Mycobacterium tuberculosis (MTB) is a common cause of pulmonary disease in HIV-infected patients. Normal alveolar macrophages (AM) phagocytize MTB and are then activated by cytokines to kill ingested MTB. We have previously shown that HIV alveolar AM are intrinsically resistant to MTB infection compared to normal AM, likely due to an AM-activating factor secreted by alveolar T cells. In this work, we examined the ability of concentrated BAL from HIV-infected subjects to activate AM to kill MTB.
Methods BAL from HIV-infected subjects before and after starting antiretroviral therapy were concentrated 5 times using 10 kD spin columns and then cultured with normal AM for 24 hours. Virulent and avirulent MTB at an MOI of 1:1 was then added and subsequent infection determined using a BACTEC methodology. BAL cytokine concentrations were measured using a cytometric bead array assay system. Time to initial and maximal infection of the AM by MTB was assessed.
Results Virulent and avirulent MTB grew equally well in AM not treated with HIV BAL. However, pretreatment with HIV BAL significantly delayed AM infection (both initial and maximal) by avirulent MTB compared to virulent MTB (initial infection: 12.2 ± 0.3 days vs 9.8 ± 0.3 days, p < .001; maximal infection measured at day 16: 0/39 avirulent vs 34/39 virulent, p < .001). There was not a significant correlation between levels of IFN-g in BAL and time to initial infection by MTB. While treatment with antiretroviral agents lowered IFN-g concentrations in BAL, there was no difference in BAL from untreated compared to treated subjects in the ability to prime AM against MTB. Conclusions: BAL from HIV-infected subjects primes AM against infection against avirulent MTB but not virulent MTB. This is consistent with the known sensitivity of avirulent MTB to macrophage activating cytokines. The lack of correlation between BAL IFN-g concentrations and the ability to prime AM against MTB suggests that other soluble factors are involved and are currently under investigation.
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