Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection

Annexin A1: shifting the balance towards resolution and repair

“…These properties confirm the importance of ANXA1 and Ac2-26 in mediating host defense and resolution of inflammation (Buckley et al , 2014; Serhan, 2014; Vago et al , 2016). Additionally, ANXA1 contributes to the transfer of antigens from apoptotic vesicles to dendritic cells for activation of CD8 + T cells (Tzelepis et al , 2015). ANXA1 in fact, controls the immune response to Mycobacterium tuberculosis infection (Tzelepis et al , 2015).…”

“…Additionally, ANXA1 contributes to the transfer of antigens from apoptotic vesicles to dendritic cells for activation of CD8 + T cells (Tzelepis et al , 2015). ANXA1 in fact, controls the immune response to Mycobacterium tuberculosis infection (Tzelepis et al , 2015). A recent study also identified release of ANXA1 by murine macrophages expressing purigenic P2X7 receptor that contribute to its pro-resolving response (de Torre-Minguela et al , 2016).…”

Alveolar macrophages and type I IFN in airway homeostasis and immunity

“…By contrast, avirulent Mtb promotes AMw production of PGE2, which prevents necrosis and leads to apoptosis, thereby limiting bacterial survival. In this new paradigm: (i) the balance between PGE2 and LXA4 determines whether infected AMw undergo apoptosis or necrosis; (ii) the induction levels of these lipids can be modulated by virulent Mtb to their advantage; (iii) the induction of necrosis provides an exit mechanism for virulent Mtb associated with delayed initiation of adaptive immunity [52][53][54]; and (iv) the induction of apoptosis enhances innate [55] and adaptive immunity [56] to Mtb infection. Interestingly, an elegant study by Mayer-Barber and others showed that shifting the balance from 5-lipoxygenase (e.g., LXA4) towards PGE2 inhibited type I IFN, leading to a reduction of IL-10 and IL-1 receptor antagonist production and a concomitant increase in IL-1 production.…”

Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis-infected macrophages

“…Apoptosis and necrosis are two major forms of cell death that play a critical role in immunity to infection by Mycobacterium tuberculosis ( Mtb) (1). These distinct cell death modalities of macrophages (Mφ) directly affect control of Mtb growth and dissemination (2–4) as well as antigen specific T cell mediated immunity via cross-presentation (5–8). Thus it is not surprising that virulent strains of Mtb have developed mechanisms that allow evasion of Mφ apoptosis by inducing necrosis (1).…”