Decreased phagocytic capacity accompanied by autophagy activation in
blood monocytes of tuberculosis patients
Abstract
Developing host-directed therapies against resistant tuberculosis
requires a better understanding of the changes in the innate immune
response of the peripheral blood monocytes. Here, we investigated the
phagocytic capacity of blood phagocytes, the changing of the mammalian
target of rapamycin (mTOR) pathway and autophagy process of circulating
monocytes in untreated tuberculosis patients. Phagocytic capacity of
blood phagocytes and the expression of key regulators of the mTOR
pathway were analysed using flow cytometry. We detected the mRNA and
protein expression of autophagy proteins using RT-PCR and capillary
western blotting. Compared with healthy controls, the increase of
monocytes phagocytizing E.coli was lower in tuberculosis patients after
37°C activation (15.46% vs. 23.31%); The percentages of Rheb+ and
mTOR+ Raptor+ circulating monocytes were higher, while that of AMPK+
monocytes were lower. Although ATG5 and ATG12 mRNA expression increased,
the protein complex expression was decreased in the monocytes of
tuberculosis patients. Beclin-1 and ULK1 Ser 757 levels were increased
at both transcriptional and protein levels; LC3 II protein level also
was higher. Our current study suggests a decrease in the phagocytic
capacity of circulating monocytes, accompanied by autophagy activation
in active tuberculosis patients.