Involvement of Mesenchymal Stem Cells in Oral Mucosal Bacterial Immunotherapy

Abstract

Recent clinical observations indicate that bacterial vaccines induce cross-protection against infections produced by different microorganisms. MV130, a polyvalent bacterial sublingual preparation designed to prevent recurrent respiratory infectious diseases, reduces the infection rate in patients with recurrent respiratory tract infections. On the other hand, mesenchymal stem cells (MSCs) are key cell components that contribute to the maintenance of tissue homeostasis and exert both immunostimulatory and immunosuppressive functions. Herein, we study the effects of MV130 in human MSC functionality as a potential mechanism that contributes to its clinical benefits. We provide evidence that during MV130 sublingual immunization of mice, resident oral mucosa MSCs can take up MV130 components and their numbers remain unchanged after vaccination, in contrast to granulocytes that are recruited from extramucosal tissues. MSCs treated in vitro with MV130 show an increased viability without affecting their differentiation potential. In the short-term, MSC treatment with MV130 induces higher leukocyte recruitment and T cell expansion. In contrast, once T-cell activation is initiated, MV130 stimulation induces an up-regulated expression of immunosuppressor factors in MSCs. Accordingly, MV130-primed MSCs reduce T lymphocyte proliferation, induce the differentiation of dendritic cells with immunosuppressive features and favor M2-like macrophage polarization, thus counterbalancing the immune response. In addition, MSCs trained with MV130 undergo functional changes, enhancing their immunomodulatory response to a secondary stimulus. Finally, we show that MSCs are able to uptake, process and retain a reservoir of the TLR ligands derived from MV130 digestion which can be subsequently transferred to dendritic cells, an additional feature that also may be associated to trained immunity.

Human Periodontal Ligament Stem Cells Response to Titanium Implant Surface: Extracellular Matrix Deposition

“…Oral MSCs are adult stromal cells, which are distinguished by their ability to self-renew and to give rise to different cell lines (bone, fat, chondrocytes, muscles, neurons, islet cells, liver cells) [ 9 ]. In the body, adult stem cells are responsible for regular tissue maintenance as well as regenerating new tissue parts in response to injury or disease and their business can be affected in many different ways [ 10 , 11 ]. Oral tissues such as dental pulp and periodontal ligament can be used as alternative sources of MSCs compared to the well-known adult tissues (bone marrow, adipose tissue, etc.)…”

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

“…Along the same lines, the polybacterial mucosal vaccine MV130 has been shown to be effective in preventing RTI recurrences in either adults ( Alecsandru et al., 2011 ; García González and Arrutia Díez, 2019 ) or children ( Nieto et al., 2021 ). Although the action of MV130 has been studied in different cell types ( Cirauqui et al., 2018 ; Molero-Abraham et al., 2019 ; Vázquez et al., 2020 ), a clear mechanism of protection is still unidentified. Prevention of RTI recurrences in children points to an antiviral effect, as wheezing attacks in young children are predominantly linked to respiratory virus infections ( Jartti et al., 2019 ; Meissner, 2016 ; Le Souëf, 2018 ).…”

“…Moreover, in a phase 3 randomized, double-blind, placebo-controlled trial (NCT01734811), children treated with MV130 showed an important reduction in the incidence and severity of recurrent wheezing ( Nieto et al., 2021 ), a condition associated with viral infections ( Jartti et al., 2019 ; Le Souëf, 2018 ). The immunomodulatory properties of MV130 have been studied on dendritic cells (DCs) ( Cirauqui et al., 2018 ), oral epithelial cells ( Molero-Abraham et al., 2019 ), and mesenchymal stem cells ( Vázquez et al., 2020 ). However, the mechanisms underlying the broad anti-infectious protection provided by MV130 remain largely unknown.…”

Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Traumatic Hemorrhagic Shock Induced Hepatic Injury via IL-10/PTPN22-Mediated M2 Kupffer Cell Polarization

“…MSCs have attracted considerable attention in various fields of medicine (45). However, research on the safety and effectiveness of the clinical application of MSCs is still in the early stages and many obstacles remain to be addressed, such as how to optimize the reparative potential of MSCs, how to regulate their abnormal proliferation and tumorigenesis ability, and how to regulate the relationship between MSCs and other immune cells (46)(47)(48). Potter found that MSC and MSC-EVs attenuate lung injury after THS by regulating the GTPase RhoA (49).…”