• Mast cells
• Tuberculosis
• inflammation
• innate cell
• lung

• R01 AI111914 NIAID NIH HHS
• R01 AI123780 NIAID NIH HHS
• R01 AI134236 NIAID NIH HHS
• R01 HL105427 NHLBI NIH HHS

• bacterial infections
• degranulation
• immunomodulation
• innate immunity
• mast cell

• Humans
• Animals
• Mice
• Hypersensitivity
• Anti-Infective Agents/metabolism
• Cytokines/metabolism
• Immunoglobulin E
• Immunity, Innate
• Mast Cells
• Nerve Tissue Proteins/metabolism
• Receptors, Neuropeptide/metabolism
• Receptors, G-Protein-Coupled/metabolism

The immunologic mechanisms that contribute to the response to Mycobacterium tuberculosis infection still represent a challenge in the clinical management and scientific understanding of tuberculosis disease. In this scenario, the role of the different cells involved in the host response, either in terms of innate or adaptive immunity, remains key for defeating this disease. Among this coordinated cell response, mast cells remain key for defeating tuberculosis infection and disease. Together with its effector’s molecules, membrane receptors as well as its anatomical locations, mast cells play a crucial role in the establishment and perpetuation of the inflammatory response that leads to the generation of the granuloma during tuberculosis. This review highlights the current evidences that support the notion of mast cells as key link to reinforce the advancements in tuberculosis diagnosis, disease progression, and novel therapeutic strategies. Special focus on mast cells capacity for the modulation of the inflammatory response among patients suffering multidrug resistant tuberculosis or in co-infections such as current COVID-19 pandemic.

• anti-TB therapy
• biomarker
• co-infection
• disease control
• disease progression
• histamine
• mast cells
• tuberculosis

• Macropinocytosis
• Mast cell extracellular traps
• Mast cells
• Mycobacterium bovis Bacillus Calmette Guerin
• Phagocytosis
• Reactive oxygen species

• Mycobacterium tuberculosis
• catalase
• mast cell
• mast cell extracellular trap
• tuberculosis

• Mycobacterium tuberculosis
• degranulation
• extracellular traps
• granuloma
• infection
• mast cells

• MR/N001427/1 Medical Research Council

In this study, we investigated the role of a matricellular protein galectin-9 (Gal-9) in pleural effusion related to tuberculosis (TB). Plasma and pleural fluid of a patient with extrapulmonary TB were analyzed for cytokine content by ELISA and Luminex. Peripheral blood mononuclear cells (PBMCs) and pleural fluid cells (PFCs) were examined for interferon-γ (IFN-γ) secretion by the enzyme-linked immunospot (ELISPOT) assay or IFN-γ ELISA, for apoptosis and necrosis by Cell Death Detection ELISA, and also underwent cell sorting. The results indicate that compared to plasma, pleural fluid had increased levels of IFN-γ (1.6 vs. 55.5 pg/mL), IL-10, IL-12p40, vascular endothelial growth factor (VEGF), and Gal-9 (3.0 vs. 936.0 pg/mL), respectively. PFCs culture supernatant exhibited higher concentration of Gal-9 compared to PBMCs in culture, consistent with enriched Gal-9 staining in the granuloma that is in closer vicinity to PFCs compared to PBMCs. PFCS displayed higher IFN-γ secretion after stimulation with TB antigens ESAT-6/CFP-10. Furthermore, in PFCs, Gal-9 alone could stimulate IFN-γ synthesis in culture or ELISPOT, which was inhibited by a Gal-9 antagonist lactose, and which may promote apoptosis and necrosis. These findings suggest that Gal-9 could modulate immune responses and participate in immunopathology of pleural effusion during TB.

• ELISPOT
• galectin-9
• matricellular protein
• pleural effusion
• tuberculosis

Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6′-dimycolate, a glycolipid produced by Mycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes including M. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells. Mincle formed a protein complex with not only FcεRIγ but also FcεRIβ in a stable cell line expressing myc-tagged Mincle. In addition, engagement of Mincle increased the levels of protein tyrosine phosphorylation and ERK phosphorylation. A pull-down assay demonstrated that cross-linking of Mincle induced binding of FcεRIβγ subunits to the Src homology 2 domain of Syk. Pharmacological and genetic studies indicated that activation of Syk was critical for Mincle-mediated activation of phospholipase Cγ2, leading to the activation of ERK and nuclear factor of activated T cells. Moreover, engagement of Mincle efficiently induced up-regulation of characteristic mast cell genes in addition to degranulation. Taken together, our present results suggest that mast cells contribute to Mincle-mediated immunity through Syk activation triggered by association with the FcεRIβγ complex.

AIM: To study the bacteriocidal or bacteriostatic role of mast cells during infection with Mycobacterium.

METHODS: Mycobacterium marinum (M. marinum) (BAA-535/M strain) was investigated for its ability to grow at a temperature relevant to the mammalian host. Primary mast cells were differentiated from bone marrows of mice, a human mast cell line (HMC-1) and a human monocytic cell line (MonoMac6) were maintained in culture. Mice were stimulated by intraperitoneal injection of heat-killed M. marinum to study cytochemically the degranulation of peritoneal mast cells. HMC-1 cells were stimulated with M. marinum to analyse mRNA expression for inflammatory reactant genes, while HMC-1 and primary mouse mast cells were infected with M. marinum to establish in parallel cell viability (lactate dehydrogenase release and cell counts) and viable mycobacterial counts. Flow cytometry was used to assess intracellular presence of fluorescein isothiocyanate labelled M. marinum after trypan blue quenching and to measure the extent of infection-induced apoptosis or necrosis in HMC-1. A GFP expressing recombinant M. marinum strain was used to assess intracellular location by fluorescence microscopy. Light microscopy of osmium tetroxide and Gram Twort stained sections of 0.5 μm and transmission electron microscopy were undertaken as sensitive methods.

RESULTS: Since its isolation, M. marinum has adapted to grow at 37 °C. This study found that M. marinum infects HMC-1 cells and primary murine mast cells, where they survive, replicate, and cause dose dependent cell damage over the analysis period of up to 120 h. Amikacin was an effective aminoglycoside antibiotic to eliminate extracellular or membrane attached M. marinum in order to adequately quantify the intracellular bacterial loads. In vivo, intraperitoneal injection of heat-killed M. marinum led to the release of mast cell granules in mice. HMC-1 cells stimulated with M. marinum showed a biphasic pattern of increased mRNA expression for LL-37 and COX-2/TNF-α during 24 h of stimulation. In HMC-1, M. marinum localised to the cytoplasm whereas in primary mast cells, M. marinum were found in vacuoles.

CONCLUSION: The effector role of mast cells in infection with M. marinum can be studied in vitro and in vivo.

• Mast cells
• Mycobacterium marinum
• Microscopy
• Infection
• Degranulation

Lungs are indispensable organs for the respiratory process, and maintaining their homeostasis is essential for human health and survival. However, during the lifetime of an individual, the lungs suffer countless insults that put at risk their delicate organization and function. Many cells of the immune system participate to maintain this equilibrium and to keep functional lungs. Among these cells, mast cells have recently attracted attention because of their ability to rapidly secrete many chemical and biological mediators that modulate different processes like inflammation, angiogenesis, cell proliferation, etc. In this review, we focus on recent advances in the understanding of the role that mast cells play in lung protection during infections, and of the relation of mast cell responses to type I hypersensitivity-associated pathologies. Furthermore, we discuss the potential role of mast cells during wound healing in the lung and its association with lung cancer, and how mast cells could be exploited as therapeutic targets in some diseases

• Allergic inflammation
• cancer
• lungs
• mast cells
• pathogens
• wound healing.

The role of mast cells (MCs) in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator) or disodium cromoglycate (DSCG, MC inhibitor). Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P < 0.01), spleen (P < 0.05), and mesentery (P < 0.05) tissues, higher parasite burden in the peritoneal lavage fluids (P < 0.01), and increased levels of mRNA transcripts of T. gondii tachyzoite surface antigen 1 (SAG1) gene in the spleen and liver tissues (P < 0.01), accompanied with significantly increased Th1 cytokine (IFN-γ, IL-12p40, and TNF-α) (P < 0.01) and decreased IL-10 (P < 0.01) mRNA expressions in the liver, and increased IFN-γ (P < 0.01) and IL-12p40 (P < 0.01) but decreased TNF-α (P < 0.01) and IL-4 (P < 0.01) in the spleens of infected mice treated with C48/80 at day 9-10 p.i. Whereas mice treated with DSCG had significantly decreased tissue lesions (P < 0.01), lower parasite burden in the peritoneal lavage fluids (P < 0.01) and decreased SAG1 expressions in the spleen and liver tissues (P < 0.01), accompanied with significantly increased IFN-γ (P < 0.01) and IL-12p40 (P < 0.05) in the liver, and decreased IFN-γ (P < 0.05) and TNF-α (P < 0.01) in the spleens; IL-4 and IL-10 expressions in both the spleen and liver were significantly increased (P < 0.01) in the infected mice treated with DSCG. These findings suggest that mediators associated with the MC activation may play an important role in modulating acute inflammatory pathogenesis and parasite clearance during T. gondii infection in this strain of mice. Thus, MC activation/inhibition mechanisms are potential novel targets for the prevention and control of T. gondii infection.

• Animals
• Cell Degranulation/immunology
• Cromolyn Sodium/pharmacology
• Cytokines/genetics
• Cytokines/metabolism
• Female
• Liver/immunology
• Liver/parasitology
• Liver/pathology
• Mast Cells/drug effects
• Mast Cells/immunology
• Mesentery/immunology
• Mesentery/parasitology
• Mesentery/pathology
• Mice
• Spleen/immunology
• Spleen/parasitology
• Spleen/pathology
• Th1 Cells/immunology
• Th1 Cells/metabolism
• Th2 Cells/immunology
• Th2 Cells/metabolism
• Toxoplasma/immunology
• Toxoplasmosis, Animal/drug therapy
• Toxoplasmosis, Animal/immunology
• Toxoplasmosis, Animal/mortality
• Toxoplasmosis, Animal/parasitology

• asthma
• host defense
• innate immunity
• mast cells
• mycoplasma pneumoniae

• Animals
• Asthma/complications
• Host-Pathogen Interactions/immunology
• Hypersensitivity/immunology
• Hypersensitivity/microbiology
• Immunity, Innate
• Interleukin-6/immunology
• Lung/immunology
• Lung/microbiology
• Male
• Mast Cells/immunology
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mycoplasma pneumoniae
• Pneumonia, Mycoplasma/complications
• Pneumonia, Mycoplasma/immunology

• P01 HL073907 NHLBI NIH HHS
• P01HL0703907 NHLBI NIH HHS

• Age Factors
• Animals
• Aromatase/biosynthesis
• Aromatase/genetics
• Chronic Disease
• Disease Models, Animal
• Estrogens/biosynthesis
• Humans
• Inflammation
• Male
• Mast Cells/immunology
• Mast Cells/pathology
• Mice
• Mice, SCID
• Mice, Transgenic
• Precancerous Conditions/etiology
• Precancerous Conditions/metabolism
• Precancerous Conditions/pathology
• Prostatic Intraepithelial Neoplasia/etiology
• Prostatic Intraepithelial Neoplasia/metabolism
• Prostatic Neoplasms/etiology
• Prostatic Neoplasms/metabolism
• Prostatitis/etiology
• Prostatitis/metabolism
• Prostatitis/pathology
• Up-Regulation

• alcian blue
• elastic fibers
• lung
• mast cells
• mucin
• mucus
• pyronine y
• respiratory syncytial virus

• Alcian Blue/chemistry
• Animals
• Carnivora
• Disease Models, Animal
• Lung Diseases/pathology
• Mice
• Pyronine/chemistry
• Rabbits
• Rats
• Respiratory System/cytology
• Respiratory System/pathology
• Sheep
• Staining and Labeling
• Swine

• R01 AI063520 NIAID NIH HHS
• AI 063520 NIAID NIH HHS