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Review
. 2024 May 2:14:1384420.
doi: 10.3389/fcimb.2024.1384420. eCollection 2024.

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Mehrdad Moosazadeh Moghaddam  1 , Elham Behzadi  2 , Hamid Sedighian  3 , Zoleikha Goleij  3 , Reza Kachuei  4 , Mohammad Heiat  5 , Abbas Ali Imani Fooladi  3
Affiliations
Review

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Mehrdad Moosazadeh Moghaddam et al. Front Cell Infect Microbiol. .

Abstract

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

Keywords: host-directed therapy; immunomodulation; microbial infection; stem cell-derived exosomes; toll-like receptors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Different pharmaceutical agents, which can be used in host-directed therapy (HDT). These approaches lead to complete treatment of the disease or improvement of symptoms.
Figure 2
Figure 2
Structure of Toll-like receptor.
Figure 3
Figure 3
The cellular localization of Toll-like receptors (TLRs) and a variety of PAMPs and DAMPs which can specifically stimulate different TLRs. These receptors can be categorized as follows: TLRs 1, 2, 4, 5, and 6 are present on the outer surface of cells, whereas TLRs 3, 7, 8, and 9 are found within the cell, namely on endosomal membranes. Upon binding to their specific ligands, it is believed that TLRs 3, 4, 5, 7, and 9 initiate signaling through their homodimers. However, depending on the particular ligand involved, TLR2 can form heterodimers with either TLR1 or TLR6.
Figure 4
Figure 4
Intraction between PAMPs ligands and TLRs and regulating the expression of proinflammatory cytokines in the nucleus. NF-κB is activated by all TLRs to elevate the expression of proinflammatory cytokines in the nucleus. Furthermore, activation of interferon regulatory factor 3 (IRF3) by some TLRs such as TLR4 leads to upregulation of type 1 INF expression.
Figure 5
Figure 5
EVs can be classified into three primary subpopulations based on the size and biogenesis process,: (i) exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (AB). Exosomes are produced when endosomes internally budder, resulting in multivesicular bodies (MVBs) which are then released into the extracellular space following fusion with the plasma membrane. Direct outward plasma membrane budding produces MVs. The AB is membrane blebs produced during cell apoptosis.
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The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
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