High levels of PF4, VEGF-A, and classical monocytes correlate with the platelets count and inflammation during active tuberculosis

Abstract

Platelets play a major role in coagulation and hemostasis; evidence supports the hypothesis that they also contribute to immunological processes. Increased platelet counts have been associated with poor prognosis in tuberculosis (TB). Platelet–monocyte aggregates have been reported in patients with TB, but it is still unclear if only one monocyte subpopulation is correlated to the platelet count; moreover, the platelet–monocyte axis has not been studied during latent tuberculosis (LTB). In this study, mononuclear cells and plasma were obtained from patients diagnosed with active drug-sensitive TB (DS-TB, n = 10) and LTB (n = 10); cytokines and growth factors levels associated to platelets were evaluated, and correlations with monocyte subpopulations were performed to identify a relationship between them, as well as an association with the degree of lung damage. Our data showed that, compared to LTB, DS-TB patients had an increased frequency of platelets, monocytes, and neutrophils. Although DS-TB patients showed no significant difference in the frequency of classical and non-classical monocytes, the classical monocytes had increased CD14 intensity of expression and frequency of TLR-2+. Furthermore, the plasma levels of angiogenic factors such as vascular endothelial growth factor (VEGF-A), platelet-derived growth factor (PDGF-BB), and platelet factor-4 (PF4), and pro-inflammatory cytokines like interleukin 6 (IL-6), interleukin 1 beta (IL-1β), and interferon-γ-inducible protein 10 (IP-10) were increased in DS-TB patients. In addition, PF-4 and VEGF-A correlated positively with the frequency of classical monocytes and the platelet count. Using a principal component analysis, we identified four groups of DS-TB patients according to their levels of pro-inflammatory cytokines, angiogenic factors, and degree of lung damage. This study establishes that there is a correlation between VEGF-A and PF4 with platelets and classical monocytes during active TB, suggesting that those cell subpopulations are the major contributors of these molecules, and together, they control the severity of lung damage by amplification of the inflammatory environment.

Latent Tuberculosis Patients Have an Increased Frequency of IFN-γ-Producing CD5+ B Cells, Which Respond Efficiently to Mycobacterial Proteins

“…In consonance with a previous report [ 21 ], the DS-TB group showed a higher platelet count than UC ( p < 0.0001) and LTB ( p < 0.0001). Similarly, DS-TB patients had a higher count of platelets than DR-TB patients ( p < 0.0004).…”

“…Regarding IL-4 levels, UC increased the level with TP stimulus [unstimulated: 2 (0.7-4); TP: 24 , p < 0.0151]. Interestingly, LTB increased IL-4 levels but under TL stimulus [0.7 (0.7-2); TL: 41 , p < 0.0106]; the DS-TB group was similar [unstimulated: 2 (0.7-3); TL: 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), p < 0.0461]. Regarding DR-TB, there were no observed changes (Figure 6D).…”

“…Thus, we evaluated the CD23 expression on B cells, and it did not show differences (Figure S2A), following the CD23 expression assessed on the CD5+ B subset (Figure 6E). Despite the IL-10 and IL-4 production by the CD5+ B cell subset, the frequency of the CD5+CD23+ subpopulation was decreased in UC and LTB patients stimulated with TP [UC: unstimulated, 52 (44-65); TP, 19 , p < 0.0285; LTB: unstimulated, 59 (57-59); TP, 25 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), p < 0.0372]. On the contrary, DR-TB patients increased the CD5+ CD23+ B cells frequency in both TP and TL stimuli [unstimulated: 46 (32-60); TP: 77 (65-94), p < 0.0324; TL: 83 (73-88), p < 0.0267] (Figure 6F).…”

Monocyte at diagnosis as a prognosis biomarker in tuberculosis patients with anemia

“…Our data, in A-TB patients, showed a significant increase in the number of platelets and monocytes in the non-cured group compared to the cured group, and, the increase in the number of monocytes in the non-cured group and the recovery of the cavity were positively correlated, consistent with reports, suggesting that our study is consistent with an immune mechanism of the platelet/monocyte axis. Although, the study showed no change in the frequency of classical and non-classical monocytes in DS-TB patients ( 35 ). Our data, in non-anemic TB patients, the number of platelets and monocytes did not change in the non-cured patients compared to the cured group, suggesting that monocytes are only a prognostic risk factor in A-TB patients and a key to our detailed analysis of A-TB monocytes.…”

“…Current research focusing on monocytes and their subsets in TB has found that CD16 monocyte is expanded in TB infection ( 33 ), while expansion of CD16 monocyte is reversed with anti-TB treatment ( 34 ). It was shown that DS-TB patients had an increased frequency of platelets and monocytes compared to LTB ( 35 ). Our data, in A-TB patients, showed a significant increase in the number of platelets and monocytes in the non-cured group compared to the cured group, and, the increase in the number of monocytes in the non-cured group and the recovery of the cavity were positively correlated, consistent with reports, suggesting that our study is consistent with an immune mechanism of the platelet/monocyte axis.…”