Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multivesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non‐hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell‐to‐cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intracellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.

IntroductionThe ability of our innate immune system to rapidly recognize and respond to invading microbes is essential for controlling infections. This is accomplished by the expression of pattern recognition receptors (PRRs) on macrophages and other leukocytes, which recognize and respond to microbial components. 1,2 The PRRs recognize a diverse set of molecules generally classified as pathogen-associated molecular patterns (PAMPs), which include proteins, glycolipids, and glycoproteins, as well as DNA and RNA. 3 The importance of this interaction has been highlighted in numerous human and animal studies, but has been most extensively studied in mice deficient in the PRRs Toll-like receptor 2 (TLR2) or TLR4, which show increased susceptibility to Gram-positive and Gram-negative bacterial infections, respectively. 4 Therefore, based on their importance in both the innate and acquired immune responses, increased interaction between PAMPs and PRRs would likely lead to improved control of an infection. Although it is well established that intracellular pathogens are relatively inaccessible to certain components of the immune system, it is also likely that PAMPs expressed by intracellular pathogens would have only limited contact with immune cells compared with PAMPs released by extracellular pathogens. However, there may be mechanisms by which microbial proteins and lipids may be released from infected cells and thus overcome, at least in part, this sequestration of PAMPs.One recently described mechanism for release of proteins and lipids from cells is through the fusion of multivesicular bodies (MVBs) with the plasma membrane and subsequent exocytosis of their cargo. The membranes of the MVBs have their origin within the endocytic network, and thus this secretion system would consist of components present within this network. This would include foreign molecules present within phagosomes that have access to the endosomal pathway and which are subsequently trafficked to the MVB. The fusion of the MVB with the plasma membrane results in the release of the internal vesicles known as exosomes into the extracellular space. Exosomes are small 50-to 100-nm diameter vesicles that are released from many different cell types. 5,6 Originally characterized as a mechanism to remove transferrin from maturing reteculoyctes, 7 exosomes derived from dendritic cells (DCs) and B cells have recently garnered considerable interest since they express both major histocompatibility class (MHC) class I and II molecules as well as costimulatory molecules, and have been shown to promote T-cell activation. [8][9][10] Treatment of patients with cancer with exosomes primed with specific tumor antigens are now in clinical trials, 11 and show promise as novel therapeutic agents. 12 Therefore, recent evidence suggests that exosomes have biological significance. Nevertheless, there remain major gaps in our knowledge of exosome biology. In the present study, we show that exosomes released from macrophages infected with different intracellular patho...

An effective immune response requires the engagement of host receptors by pathogen-derived molecules and the stimulation of an appropriate cellular response. Therefore, a crucial factor in our ability to control an infection is the accessibility of our immune cells to the foreign material. Exosomes-which are extracellular vesicles that function in intercellular communication-may play a key role in the dissemination of pathogen-as well as host-derived molecules during infection. In this review, we highlight the composition and function of exosomes and other extracellular vesicles produced during viral, parasitic, fungal and bacterial infections and describe how these vesicles could function to either promote or inhibit host immunity.