Spontaneous or Mycobacterium tuberculosis‐induced apoptotic neutrophils exert opposite effects on the dendritic cell‐mediated immune response

Abstract

Polymorphonuclear neutrophils (PMN) modulate the adaptive immune response through interactions with immature dendritic cells (iDC) while spontaneous apoptotic neutrophils (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DC maturation and the role of Mycobacterium tuberculosis (Mtb)-induced PMNapo in the cross-presentation of mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC while it is impaired by the presence of PMNapo, which abrogate Mtb-induced expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN-c release by DC and partially inhibiting Mtb-driven lymphocyte proliferation. This inhibitory effect is not observed in already Mtb-matured DC, and it involves a direct interaction between DC and PMNapo, as supernatants from PMNapo cultures do not reveal this effect. Although PMNapo do not alter Mtb/DC-SIGN interaction, they affect the intracellular signals leading to DC maturation without requiring their entry into DC. Phagocytosis of Mtb-induced PMNapo by iDC leads to lymphoproliferation, which is significantly reduced by blocking CD36 and not DC-SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our findings suggest that the inflammatory milieu is subjected to a fine balance between non-infected and Mtb-induced PMNapo: non-infected PMNapo limiting inflammation and Mtb-induced PMNapo generating a specific immune activity.

Mycobacterium bovis BCG‐infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice

“…They may also be able to acquire antigens from apoptotic vesicles as demonstrated for macrophages [45]. More detailed analysis of the contribution of live and apoptotic neutrophils to this cross-presentation is required [46]. Whatever the mechanism, these data clearly demonstrate that neutrophils could help DC to cross-present BCG antigens to naive CD4 + and CD8 + T cells.…”

Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease

“…Neutrophil activity may modify DC maturation and activation (64)(65)(66) and enhance the release of IL-12 and TNF-a from DCs (65), suggesting that neutrophil responses play a crucial role in influencing DCs to induce Th1 responses upon contact with T cells. Furthermore, neutrophils can present Ag to T cells and induce T cell proliferation and cytokine release (67,68).…”

Dendritic cell activation by sensing Mycobacterium tuberculosis–induced apoptotic neutrophils via DC-SIGN

“…We observed that PMN Mtb trigger a cell-cell contactdependent DC maturation, whereas PMN Apo is inhibitory for DC maturation and could play a important part in maintaining peripheral tolerance [35,36]. Both PMN Apo and PMN Mtb interacted with DCs, but only a few cells were actually internalized by DCs, a finding supported by the observation that apoptotic PMNs are phagocytosed only when presented to the IDCs in vast excess [10].…”