Phagocytosis–Inflammation Crosstalk in Sepsis: New Avenues for Therapeutic Intervention

Abstract

Phagocytosis is a complex process by which cells within most organ systems remove pathogens and cell debris. Phagocytosis is usually followed by inflammatory pathway activation, which promotes pathogen elimination and inhibits pathogen growth. Delayed pathogen elimination is the first step in sepsis development and a key factor in sepsis resolution. Phagocytosis thus has an important role during sepsis and likely contributes to all of its clinical stages. However, only a few studies have specifically explored and characterized phagocytic activity during sepsis. Here, we describe the phagocytic processes that occur as part of the immune response preceding sepsis onset and identify the elements of phagocytosis that might constitute a predictive marker of sepsis outcomes. First, we detail the key features of phagocytosis, including the main receptors and signaling hallmarks associated with different phagocytic processes. We then discuss how the initial events of phagosome formation and cytoskeletal remodeling might be associated with known sepsis features, such as a cytokine-driven hyperinflammatory response and immunosuppression. Finally, we highlight the unresolved mechanisms of sepsis development and progression and the need for cross-disciplinary approaches to link the clinical complexity of the disease with basic cellular and molecular mechanisms.

The Clinical Value of GDF15 and Its Prospective Mechanism in Sepsis

“…Phagocytosis is also closely related to inflammation and immune response. To some extent, low phagocytosis means a high risk of infection and poor clinical outcomes ( 49 ). In the late stage of sepsis, the phagocytic function of macrophages and monocytes are damaged and the immune system is paralyzed, resulting in the failure of timely removal of pathogens in patients and aggravating the disease.…”

SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry

“…Although macrophages offer protection against infection by playing a key role in the immune defense system, they can cause serious immunopathology. Among the immunopathological conditions directly related to the improper functioning of macrophages, which turn from friends into life-threatening enemies, are sepsis ( 5 ), cancer ( 81 ), diabetes ( 82 , 83 ), and heart disease ( 84 ).…”

“…The act of phagocytosis is a fundamental process that is playing a key role in immunity ( 4 ). Phagocytosis can be accompanied by activation of the inflammatory pathway, which contributes to the elimination of the pathogen by inhibiting its spread ( 5 ).…”

Lung Organoids—The Ultimate Tool to Dissect Pulmonary Diseases?

“…Sepsis is a condition characterized by life-threatening organ dysfunction, and is caused by the host response to infection, most commonly by bacteria ( Minasyan, 2019 ; Reyes et al, 2020 ) but also by some viruses ( Singer et al, 2016 ; Hortova-Kohoutkova et al, 2020 ; Hortova-Kohoutkova et al, 2021 ). In the respiratory system, sepsis manifests clinically as acute lung injury (ALI) or, the more severe acute respiratory distress syndrome (ARDS) ( Sevransky et al, 2009 ; Angus and van der Poll, 2013 ).…”