Neutrophil‐T cell crosstalk and the control of the host inflammatory response

Abstract

While fundamental in their innate role in combating infection and responding to injury, neutrophils are emerging as key modulators of adaptive immune responses. Such functions are attained via both soluble and nonsoluble effectors that enable at least two major downstream outcomes: first, to mediate and control acute inflammatory responses and second, to regulate adaptive immunity and ultimately promoting the development and maintenance of immune tolerance either by releasing immunomodulatory factors, including cytokines, or by directly interacting with cells of the adaptive immune system. Herein, we review these novel properties of neutrophils and redefine the pathophysiological functions of these fascinating multi-tasking cells, exploring the different mechanisms through which neutrophils are able to either enhance and orchestrate T cell pro-inflammatory responses or inhibit T cell activity to maintain immune tolerance.

Unbiased single cell spatial analysis localises inflammatory clusters of immature neutrophils-CD8 T cells to alveolar progenitor cells in fatal COVID-19 lungs

“…A consequence could be that the production of type I IFN, [and other monocyte-specific cytokines like IL-6 and TNF-α (as reviewed by, (Bert et al, 2022;Costa et al, 2019)], combined to impact on regeneration of alveolar epithelium. It is also possible that type I IFN production from these monocytes causes upregulation of ACE2, thereby sustaining viral entry and alveolar epithelial damage (Ziegler et al, 2020).…”

Neutrophils in Cancer and Potential Therapeutic Strategies using Neutrophil-derived Exosomes

“…Accordingly, increase in CD8+ T cell response and reduction in tumor growth in the murine lung cancer system can be achieved by inhibition of IL17 production in CD11b+Ly6G+ neutrophils [71]. On the other hand, CD66b+ neutrophil infiltration is associated with CD8+ T cell infiltration, colocalization and improved responsiveness of CD8+ T cells to TCR stimulation [72] in colorectal cancer [73],indicating that these cells may be utilized for promoting antitumor immunity. Neutrophils can be activated by CD64, CD32a, CD16a via IgG-based antibodies.…”

Neutrophils and their friends

“…Depending on the magnitude of the provocation, neutrophils can sustain or terminate tissue damage secondary to inflammation. Interactions with T‐cells, either directly or indirectly via dendritic cells, extend the sphere of influence of neutrophils beyond the acute inflammatory response and serve as a gateway to shaping adaptive immunity and to contributing to the development and maintenance of immune tolerance, as discussed in detail by Bert and colleagues 3 . Furthermore, in the tumor microenvironment (TME), neutrophil‐mediated responses can dampen or promote tumor progression, and communication in this setting is bidirectional, with neutrophils and malignant cells signaling reciprocally to modulate the inflammatory tone in the tumor bed.…”

“…Recruited to sites of infection and tissue damage, neutrophils engage with tissue-based cells, including endothelial and epithelial cells, as well as other circulating cells such as platelets and T-cells. 2,3 Depending on the magnitude of the provocation, neutrophils can sustain or terminate tissue damage secondary to inflammation. focus on those that participate in pattern recognition, a critical element in host defense pathways.…”