Granulocytes: New Members of the Antigen-Presenting Cell Family

Abstract

Granulocytes, the most abundant types of leukocytes, are the first line of defense against pathogen invasion. However, the plasticity and diversity of granulocytes have been increasingly revealed, especially with regard to their versatile functions in orchestrating adaptive immune responses. A substantial body of recent evidence demonstrates that granulocytes can acquire the function as antigen-presenting cells under pathological or inflammatory conditions. In addition, they can acquire surface expression of MHC class II and costimulatory molecules as well as T cell stimulatory behavior when cultured with selected cytokines. The classic view of granulocytes as terminally differentiated, short-lived phagocytes is therefore changing to phenotypically and functionally heterogeneous cells that are engaged in cross-talk with other leukocyte populations and provide an additional link between innate and adaptive immunity. In this brief review, we summarize the current knowledge on the antigen-presenting capacity of granulocyte subsets (neutrophils, eosinophils, and basophils). Underlying mechanisms, relevant physiological significance and potential controversies are also discussed.

Keywords: MHC; antigen presentation; basophil; eosinophil; neutrophil.

Figure 1

Granulocytes acquire antigen-presenting cell (APC) features via bystander activation from neighboring professional APCs stimulating T cells. Antigen presentation initiated by dendritic cells (DCs) or other professional APCs leads to stimulation of T cells to produce cytokines (e.g., IFN-γ). This results in that granulocytes upregulate expression of MHC-II and costimulatory molecules on their surface, which enables them in turn to present antigens to T cells.

Figure 2

Potential mechanisms involved in inducing the antigen presentation capacity in granulocytes. Granulocytes can de novo synthesize MHC-II and costimulatory molecules upon stimulation by exogenous cytokines (e.g., IFN-γ, GM-CSF, and TNF) likely derived from activated T cells ①. Cytokines produced in an autocrine manner may also activate granulocytes and induce the antigen-presenting cell (APC)-associated machinery ②. In addition to de novo synthesis, neutrophils contain intracellular stores of MHC-II and costimulatory molecules, which translocate to the cell surface upon stimulation ③. Specific receptors expressed on granulocytes and T cells may mediate initial cell-to-cell contact and amplify the differentiation of granulocytes to become APCs ④. Basophils have also been shown to acquire MHC–peptide complexes from other APCs [e.g., dendritic cells (DCs)] through trogocytosis (transfer of MHC-II–peptide complexes) leading to presentation to T cells ⑤.