HLA-DR-Positive NK Cells Expand in Response to Mycobacterium Tuberculosis Antigens and Mediate Mycobacteria-Induced T Cell Activation

Abstract

NK cells play an important role in the control of tuberculosis infection: they are not only able to kill the infected cells, but also control the activity of macrophages and development of the adaptive immune response. Still, there is little information on the role of specific NK cell subsets in this network. In this study, we focused on the mycobacteria-driven responses of the NK cells expressing HLA-DR – a type of MHC class II. We have revealed that this subset is increased in the peripheral blood of patients with primary diagnosed tuberculosis, and expands in response to in vitro stimulation with ultrasonically destroyed Mycobacterium tuberculosis cells (sonicate). The expanded HLA-DR+ NK cells had less differentiated phenotype, higher proliferative activity and increased expression of NKp30 and NKp46 receptors. HLA-DR+CD56dim NK cells showed higher IFNγ production and degranulation level than the respective HLA-DR− NK cells in response to both 24 h and 7 day stimulation with sonicate, while HLA-DR+CD56bright NK cells mostly demonstarted similar high responsiveness to the same stimulating conditions as their HLA-DR−CD56bright counterparts. After preliminary incubation with destroyed mycobacteria, cytokine-activated HLA-DR-expressing NK cells were able to mediate mycobacteria-induced and HLA-DR-dependent cytokine production in autologous CD4+ T cells. Thus, functionally active HLA-DR+ cells seem to be one of the NK cell subsets providing an important link to the adaptive immunity.

Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics

“…More prominent, however, was the reduction in HLA-DR expression in SDp relative to D patients in all myeloid cell subtypes, reaching statistical significance in DN monocytes, CD16 + monocytes, and cDC2s, (q<0.05) ( Figures 3B and 3C) . Interestingly, in contrast to myeloid cells, several NK cell subtypes expressed higher levels of HLA-DR in SDp relative to D patients (q<0.05) ( Figure 3C ) , suggesting increased functional activity in SDp, as previously shown in other infectious disease models (Erokhina et al, 2018; Kust et al, 2021). While the differences in proportional myeloid cell subtype abundance and HLA-DR expression largely resolved at convalescence, increased expression of CD64 in SDp over D persisted in several myeloid subsets (p<0.05) ( Figures S3A-C, E ).…”

Dendritic cell-Natural Killer cell Crosstalk Modulates T cell activation in Response to Influenza A Viral Infection

“…HLA-DR + NK cell subsets have been found in both humans and mice and present under steady-state conditions and a range of diseases (40). For example, an HLA-DR + NK cell subset was found to be expanded in the peripheral blood of patients with primary tuberculosis (41,70). The CD56 dim NK cell subset from HIV-infected individuals displayed elevated HLA-DR expression and impaired IFN-γ production compared to uninfected controls (71).…”

“…The copyright holder for this preprint this version posted August 13, 2022. ; https://doi.org/10.1101/2022.08.12.503177 doi: bioRxiv preprint Expression of HLA-DR is generally restricted to professional antigen-presenting cells-DCs, macrophages, and B cells-although its expression has been documented on NK cells (40). For example, an HLA-DR + NK cell subset was found to be expanded in the peripheral blood of patients with primary tuberculosis and to mediate cytokine production by CD4 + T cells (41). We therefore investigated HLA-DR expression on either NK cells alone or in co-culture with MoDCs at 7 or 24 HPI.…”

“…13 patients with primary tuberculosis (41,70). The CD56 dim NK cell subset from HIV-infected individuals displayed elevated HLA-DR expression and impaired IFN-γ production compared to uninfected controls (71).…”

Yield, NNS and prevalence of screening for DM and hypertension among pulmonary tuberculosis index cases and contacts through single time screening: A contact tracing-based study

“…However, chronic diseases in their family contacts PLOS ONE also should be properly managed because we observed a significant proportion of prediabetes and prehypertension in these participants who were considered a substitute for the general population. Furthermore, the household contacts might carry similar susceptible genes with their index cases, such as speckle 110 (SP110), or human leukocyte antigen (HLA), which might be the possibly susceptible genes to the occurrence of DM or TB disease [36][37][38].…”