PDL1 expression on monocytes is associated with plasma cytokines in
Tuberculosis and HIV
Abstract
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.