Role of innate and adaptive arms of immunosuppressive players in sepsis

CellsNormal functionsImmunosuppressive functions
Players of innate immunity
NeutrophilsNeutrophils are potent phagocytic cells showing the antimicrobial activity through oxidative killing and granule product-mediated killing

  • Fail to expand neutrophil counts

  • Increased immature neutrophils

  • Delayed clearance of NETs

  • Increased secretion of IL-10

  • Reduced apoptosis

  • Reduced ROS production

  • Reduced expression adhesion markers

  • Reduced nitric oxide release

MonocytesMonocytes are the source of other vital elements of the immune system, such as DCs and macrophages. Monocytes recognize the pathogens through the PRRs and phagocyte them. They work as APCs, secrete cytokines and chemokines, and activate Th cells

  • Reduced HLA-DR expression

  • Increased apoptosis

  • Increased secretion of IL-10

  • Reduced T cell proliferation

  • Reduced surface expression of CD80 and CD86

MDSCsMDSCs are a heterogeneous population of cells of myeloid origin. They are differentiated into granulocytes, macrophages, and DCs. MDSCs are potent suppressors of T cells proliferation and activation. They are primarily beneficial for restoring homeostasis after inflammation. Because of their ability to suppress adaptive immunity, MDSCs can also ameliorate autoimmune diseases and semi-allogenic responses

  • Reduced T cell proliferation

  • Reduced cytotoxic functions of CD8 T cells

  • Increased secretion of IL-10

  • Increased apoptosis

  • Enhanced Treg cells production

  • Reduced differentiation to mature granulocytes, macrophages, and DCs

  • Enhanced production of immature populations of MDSCs

DCsDCs are professional APCs and play important roles in regulating the innate and adaptive immune responses

  • Reduced T cells proliferation

  • Reduced cytokine secretions

  • Increased apoptosis

  • Reduced cell surface activation markers

NK cellsNK cells are effector lymphocytes having cytotoxicity and cytokines secreting effector functions. NK cells control several types of microbial infections and tumors by limiting their spread and subsequent tissue damages

  • Reduced cytotoxic functions

  • Increased apoptosis

  • Reduced cytokine secretion

Players of adaptive immunity
CD4+ Th cellsTh cells are major components of adaptive immunity, recognize the pathogens through class II MHC, and activate the B cells to secrete Abs and macrophages to destroy the ingested microbes. They also activate the cytotoxic CD8+ T cells during inflammation and help in recruiting the PMNs, basophils, and eosinophils to the loci of infection and inflammation

  • Shift in polarity of Th cells from Th1 to Th2

  • Increased Th cells exhaustion

  • Reduced surface expression of CD28

  • Increased apoptosis

  • Reduced cytokine secretion

  • Reduced Th cells activation and proliferation

  • Increased levels of Treg cells

CD8+ Tc cellsCytotoxic CD8+ T cells kill the infected and cancerous cells much like the NK cells do. They recognize the antigens, processed and presented them through class I MHC molecule, and get activated. The activated CD8 T cells secrete perforins and granzymes, and eliminate the intracellular pathogens and cancerous cells

  • Increased CD8 T cells exhaustion

  • Reduced cytokine secretion

  • Increased apoptosis

  • Reduced CD8 T cells proliferation

B cellsB cells fight against extracellular pathogens by secreting too specific Abs against antigen. B cells also perform the role of APCs and activate the Th cells in clearing the infected cells and cancerous cells

  • Reduced Ab production

  • Increased exhaustion of B cells

  • Increased apoptosis

Abs: antibodies; APCs: antigen-presenting cells; HLA: human leukocytes antigen; IL-10: interleukin-10; MHC: major histocompatibility complex; PMNs: polymorphonuclear neutrophils; Tc: cytotoxic T; Th: T helper; Treg: T regulatory