Introduction: PDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studies. Method HIV (n=35), TB (n=34) and TBHIV co-infected patients (n=12), primarily treatment naïve and apparently healthy controls (n=39) were recruited. Monocyte subsets were evaluated for PDL1 expression by flow cytometry; plasma TNFα, IL6, IP10, IL10 were measured by Luminex; and cytokine mRNA from purified monocytes quantitated by qPCR. The association of PDL1 with cytokines, clinical and microbial indices, including HIV viral load, TB smear microscopy and TB urinary lipoarabinomannan (LAM) were assessed. Results: Monocyte expression of PDL1 was significantly higher in TB, HIV and TBHIV co-infected patients compared with healthy controls (p=0.0001), with the highest levels in TBHIV co-infected patients. The highest expresser of PDL1 was intermediate (CD14+CD16+) monocytes in all participant groups. PDL1 moderately correlated with viral load and smear positivity in HIV and TB respectively, whereas weakly with LAM in TBHIV co-infection. PDL1 levels strongly correlated with plasma TNFα, IL6, IP10 and IL10 level in TB subjects, and TNFα and IP10 in HIV patients. However, cytokine mRNA from purified monocytes showed no association with either plasma cytokines or monocyte PDL1, implying that if cytokines modulate PDL1, there are likely not originating from circulating monocytes themselves. These results underscore the importance of further characterization of multiple monocyte subsets and their phenotypic and functional differences in different disease states.

Background Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers. Methods Messenger RNA (mRNA) were analysed in a total of 64 samples collected from apparently healthy children and adolescents, who were latently infected with tuberculosis (n=32) or non-infected (n=32) and were selected using purposive sampling to compare the relative expressions of selected TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9), using quantitative real-time polymerase chain reaction (qRT-PCR). Specific primers and florescent labelled probes were used to detect the expression of these markers in peripheral blood; a comparative threshold cycle method was used to describe fold change in the relative expression of TLR genes. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant. Results An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene. Conclusions An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.