Activated Mesenchymal Stem Cells Interact with Antibiotics and Host Innate Immune Responses to Control Chronic Bacterial Infections

The SARS-CoV-2, the virus that causes COVID-19, has infected millions of people worldwide. The symptoms of this disease are primarily due to pulmonary involvement, uncontrolled tissue inflammation, and inadequate immune response against the invader virus. Impaired interferon (IFN) production is one of the leading causes of the immune system’s inability to control the replication of the SARS-CoV-2. Mitochondria play an essential role in developing and maintaining innate cellular immunity and IFN production. Mitochondrial function is impaired during cellular stress, affecting cell bioenergy and innate immune responses. The mitochondrial antiviral-signaling protein (MAVS), located in the outer membrane of mitochondria, is one of the key elements in engaging the innate immune system and interferon production. Transferring healthy mitochondria to the damaged cells by mesenchymal stem cells (MSCs) is a proposed option for regenerative medicine and a viable treatment approach to many diseases. In addition to mitochondrial transport, these cells can regulate inflammation, repair the damaged tissue, and control the pathogenesis of COVID-19. The immune regulatory nature of MSCs dramatically reduces the probability of an immune rejection. In order to induce an appropriate immune response against the SARS-CoV-2, we hypothesize to donate mitochondria to the host cells of the virus. We consider MSCs as an appropriate biological carrier for mitochondria. Besides, enhancing the expression of MAVS protein in MSCs and promoting the expression of SARS-CoV-2 viral spike protein as a specific ligand for ACE2+ cells will improve IFN production and innate immune responses in a targeted manner.

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Neutrophil gelatinase-associated lipocalin and innate immune responses to bacterial infections

Medical Microbiology and Immunology ◽

10.1007/s00430-015-0394-1 ◽

2015 ◽

Vol 204 (4) ◽

pp. 471-479 ◽

Cited By ~ 38

Author(s):

Dimitrios Nasioudis ◽

Steven S. Witkin

Keyword(s):

Immune Responses ◽

Bacterial Infections ◽

Innate Immune ◽

Innate Immune Responses ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

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Infection triggers tumor regression through activation of innate immunity in Drosophila

10.1101/552869 ◽

2019 ◽

Author(s):

Camille Jacqueline ◽

Jean-Philippe Parvy ◽

Dominique Faugère ◽

François Renaud ◽

Dorothée Missé ◽

...

Keyword(s):

Immune Responses ◽

Tumor Size ◽

Bacterial Infections ◽

Tumor Regression ◽

Acute Infection ◽

Innate Immune ◽

Immune Gene ◽

Infectious Agents ◽

Innate Immune Responses

AbstractThe pioneering work of Dr. William Coley has shown that infections can stimulate the immune system and improve tumor growth control. However, the immune mechanisms responsible for the protective role of infectious agents have still not been identified. Here, we investigated the role of innate immune pathways in tumor regression by performing experimental infections in genetically modified Drosophila that develop invasive neoplastic tumors. After quantifying tumor size, through image processing, and immune gene expression with transcriptomic analyses, we analyzed the link between tumor size and pathogen-induced immune responses thanks to a combination of statistical and mathematical modeling. Drosophila larvae infected with a naturally-occurring bacterium showed a smaller tumor size compared to controls and fungus-infected larvae, thanks to an increase expression of Imd and Toll pathways. Our mathematical model reinforces this idea by showing that repeated acute infection could results in an even higher decrease in tumor size. Thus, our study suggests that infectious agents can induce tumor regression through the alteration of innate immune responses. This phenomenon, currently neglected in oncology, could have major implications for the elaboration of new preventive and immunotherapeutic strategies.One Sentence SummaryBacterial infections can decrease cancer cell accumulation through stimulation of innate immune responses.

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Macrophage migration inhibitory factor and innate immune responses to bacterial infections

Critical Care Medicine ◽

10.1097/00003246-200107001-00006 ◽

2001 ◽

Vol 29 ◽

pp. S13-S15 ◽

Cited By ~ 45

Author(s):

Céline Froidevaux ◽

Thierry Roger ◽

Christian Martin ◽

Michel P. Glauser ◽

Thierry Calandra

Keyword(s):

Immune Responses ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Bacterial Infections ◽

Innate Immune ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Innate Immune Responses

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Faculty Opinions recommendation of Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.12818983.14100087 ◽

2011 ◽

Author(s):

Laurence Rahme ◽

Yiorgos Apidianakis

Keyword(s):

Stem Cells ◽

Immune Responses ◽

Innate Immune ◽

Intestinal Stem Cells ◽

Innate Immune Responses ◽

Mapk Signalling

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Innate Immune Effectors in Mycobacterial Infection

Clinical and Developmental Immunology ◽

10.1155/2011/347594 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 55

Author(s):

Hiroyuki Saiga ◽

Yosuke Shimada ◽

Kiyoshi Takeda

Keyword(s):

Immune Responses ◽

Bacterial Infections ◽

Mycobacterial Infection ◽

Innate Immune ◽

Pathogenic Microorganisms ◽

Lipocalin 2 ◽

Innate Immune Responses ◽

Active Vitamin ◽

Lectin Receptors ◽

Adaptive Immune

Tuberculosis, which is caused by infection withMycobacterium tuberculosis(Mtb), remains one of the major bacterial infections worldwide. Host defense against Mtb is mediated by a combination of innate and adaptive immune responses. In the last 15 years, the mechanisms for activation of innate immunity have been elucidated. Toll-like receptors (TLRs) have been revealed to be critical for the recognition of pathogenic microorganisms including mycobacteria. Subsequent studies further revealed that NOD-like receptors and C-type lectin receptors are responsible for the TLR-independent recognition of mycobacteria. Several molecules, such as active vitamin D3, secretary leukocyte protease inhibitor, and lipocalin 2, all of which are induced by TLR stimulation, have been shown to direct innate immune responses to mycobacteria. In addition, Irgm1-dependent autophagy has recently been demonstrated to eliminate intracellular mycobacteria. Thus, our understanding of the mechanisms for the innate immune response to mycobacteria is developing.

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Stem Cell and Macrophage Roles in Skeletal Muscle Regenerative Medicine

International Journal of Molecular Sciences ◽

10.3390/ijms221910867 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10867

Author(s):

Pasqualina Scala ◽

Laura Rehak ◽

Valentina Giudice ◽

Elena Ciaglia ◽

Annibale Alessandro Puca ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Immune Responses ◽

Muscle Tissue ◽

Peripheral Blood ◽

Cell Types ◽

Innate Immune ◽

Muscle Repair ◽

Innate Immune Responses ◽

Peripheral Cell

In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under investigation, and the discovery of pathways and cell types involved in muscle repair can open the way for novel therapeutic approaches, such as cell-based therapies involving stem cells and peripheral blood mononucleate cells. Indeed, peripheral cell infusions are a new therapy for muscle healing, likely because autologous peripheral blood infusion at the site of injury might enhance innate immune responses, especially those driven by macrophages. In this review, we summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration.

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Pluripotent stem cells are insensitive to the cytotoxicity of TNFα and IFNγ

Reproduction ◽

10.1530/rep-20-0215 ◽

2020 ◽

Vol 160 (4) ◽

pp. 547-560

Author(s):

Bohan Chen ◽

Chandan Gurung ◽

Jason Guo ◽

Chulan Kwon ◽

Yan-Lin Guo

Keyword(s):

Stem Cells ◽

Immune Responses ◽

Embryonic Stem ◽

Innate Immune ◽

Protective Mechanism ◽

Innate Immune Responses ◽

Human Escs ◽

Cell Cycle Inhibition ◽

Factor Α ◽

Oxide Synthase

Recent studies have demonstrated that embryonic stem cells (ESCs) have an underdeveloped innate immune system, but the biological implications of this finding are poorly understood. In this study, we compared the responses of mouse ESCs (mESCs) and mESC differentiated fibroblasts (mESC-FBs) to tumor necrosis factor α (TNFα) and interferons (IFNs). Our data revealed that TNFα, IFNα, IFNβ, or IFNγ alone do not cause apparent effects on mESCs and mESC-FBs, but the combination of TNFα and IFNγ (TNFα/IFNγ) showed toxicity to mESC-FBs as indicated by cell cycle inhibition and reduced cell viability, correlating with the expression of inducible nitric oxide synthase (iNOS). However, none of these effects were observed in mESCs that were treated with TNFα/IFNγ. Furthermore, mESC-FBs, but not mESCs, are vulnerable to cytotoxicity resulting from lipopolysaccharide (LPS)-activated macrophages. The insensitivity of mESCs to cytotoxicity in all cases is correlated with their lack of responses to TNFα and IFNγ. Similar to mESCs, human ESCs (hESCs) and iPSCs (hiPSCs) do not respond to TNFα and are not susceptible to the cytotoxicity of TNFα, IFNβ, or IFNγ alone or in combination that significantly affects human foreskin fibroblast (hFBs) and Hela cells. However, unlike mESCs, hESCs and hiPSCs can respond to IFNγ, but this does not cause significant cytotoxicity in hESCs and hiPSCs. Our findings in both mouse and human PSCs together support the hypothesis that attenuated innate immune responses could be a protective mechanism that limits immunologic cytotoxicity resulting from inflammatory and immune responses.

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