Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells

Abstract

Natural killer (NK) cells represent the founding members of innate lymphoid cells (ILC) and play critical roles in inflammation and the immune response. NK cell effector functions are regulated and fine-tuned by various immune modulators. Mannan (or mannose)-binding lectin (MBL), a soluble C-type lectin, is traditionally recognized as an initiator of the complement pathway. Recently, it is also considered as an immunomodulator by its interaction with kinds of immune cells. However, the effect of MBL on NK cell function remains unexplored. In this study, we found that human plasma MBL could interact directly with peripheral NK cells partially via its collagen-like region (CLR). This MBL binding markedly suppressed the interleukin-2- (IL-2-) induced inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production but increased the IL-10 production in NK cells. In addition, the expression of activation surface markers such as CD25 and CD69 declined after MBL treatment. Also, MBL impaired the proliferation and lymphokine-activated killing (LAK) of NK cells. Moreover, we demonstrated that MBL inhibited IL-2-induced signal transducers and activators of transcription 5 (STAT5) activation in NK cells. In conclusion, we have uncovered a far unknown regulatory role of MBL on NK cells, a new clue that could be important in the immunomodulatory networks of immune responses.

Establishing immune scoring model based on combination of the number, function, and phenotype of lymphocytes

“…Chromium ( 51 Cr)-release assay has the ability to detect the cytotoxicity of CD8 + T cells and NK cells [9]. We also used CFSE/PI-labeled target cells to determine the cytotoxicity of NK cells [9,10]. However, although these methods are widely used in previous studies, most of them are not suitable for clinical application due to radiation hazards, too complicated and time-consuming administration.…”

MBL2 gene polymorphisms are not related to the occurrence of cerebrovascular disease in sickle cell anemia

“…MBL activates the complement system, which acts as a defense against pathogens, but it may also cause self-damage following adverse activation (Song et al, 2014). It is known that MBL modulates proinflammatory cytokine production (Zhou et al, 2019), and it may aggravate local and systemic inflammation via complement system activation (Fiane et al, 2003;Neglia et al, 2019). Therefore, high MBL levels may mediate harmful inflammation through excessive complement activation (Bąk-Romaniszyn et al, 2020).…”

Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs

“…In addition to phagocytosis of pathogens by leukocytes and activation of the lectin complement pathway, sMBL can bind to human monocytes and attenuate the inflammatory response [44]. While looking for how sMBL can influence NK cell activity, Zhou et al suggested that human sMBL could communicate directly with peripheral NK cells through its collagen-like domain [93].…”