Mycobacterium tuberculosisH37Rv is more effective compared to vaccine strains in modulating neutrophil functions: anin vitrostudy

Abstract

Neutrophils are the primary cells contributing to initial defense against mycobacteria. Yet, little is known about the potential of various mycobacterial strains to stimulate neutrophils. This study was focused to compare the differential capacity of vaccine strains, Mycobacterium bovis bacillus Calmette-Guerin (BCG) and Mycobacterium indicus pranii (Mw), and laboratory strain H37Rv to activate and enhance neutrophil functions. The expression of phenotypic markers like Fcγ receptor, toll-like receptor (TLR), and chemokine receptor; secretion of pro-inflammatory cytokines; and the rate of apoptosis were studied in infected neutrophils. Increased expression of CD32, CD64, TLR4, and CXCR3; increased TNF-α secretion; and downregulation of early apoptosis were observed in H37Rv-infected neutrophils. Among the vaccine strains, BCG increased the expression of only CD32 on neutrophils, while Mw was comparatively ineffective. To understand the paracrine role of neutrophils, the supernatants from infected neutrophils were used to stimulate monocytes and T helper cells. The secretory molecules from all infected neutrophils increased the expression of CCR5 on monocytes, whereas only H37Rv-infected supernatant increased the expression of CCR7 on monocytes and CD69 on T cells. Thus, H37Rv was more effective in activating neutrophils and in turn stimulating monocytes and T cells. By comparison, vaccine strains were less effective in modulating neutrophil functions.

Latest Comprehensive Knowledge of the Crosstalk between TLR Signaling and Mycobacteria and the Antigens Driving the Process

“…These results confirmed that the expression of TLR4 on CD14+ monocytes, but not TLR2, is upregulated in individuals who received BCG vaccines compared with the findings in unvaccinated individuals [58]. In the case of neutrophils, Mtb stimulation also induces the expression of TLR4, TNFα, and scavenger receptors [59,60]. Another study demonstrated that TLR4 expression is required to protect mice against chronic Mtb infection.…”

Innate immune responses to Mycobacterium tuberculosis infection : How extracellular traps and trained immunity can restrict bacterial growth.

“…The role of NETs in TB is still controversial, however a correlation between plasma NET levels in patients with TB and disease severity has been observed (80). Moreover, many suggest that NETs have a role in minimizing the spread of an infection (196). We were in this project able figure 1).…”

Lipopolysaccharide from Porphyromonas gingivalis, but Not from Porphyromonas endodontalis, Induces Macrophage M1 Profile

“…Additionally, the reduction of CD64 was directly correlated with TLR2 and TLR4. In this regard, a directly proportional expression between CD64, TLR2, and TLR4 has been described in monocytes differentiated into macrophages from peripheral blood [ 71 ] and neutrophils from tuberculosis patients [ 72 ], but not in vitro macrophages differentiated to a pro-inflammatory profile. These antecedents suggest that there might be a functional relationship between the two, which would help explain the reduction in TLRs observed on the surface of LPS-stimulated macrophages in our experimental model.…”