Neuroimmunopathology of Trypanosoma cruzi-induced megaoesophagus: Is there a role for mast cell proteases?

Martins, Patrícia; Nascimento, Rodolfo Duarte; Lisboa, André de Souza; Martinelli, Patrícia Massara; Reis, Débora d’Ávila

doi:10.1016/j.humimm.2014.02.003

Cited by 10 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In BALB/c mice, the mucosal mast cell chymases mMCP-1 and mMCP-2 are substantially increased upon intestinal nematode infection [37,38]. In addition, increased numbers of chymase-positive mast cells were found in the esophagus of patients with Trypanosoma cruzi infection [39]. However, these studies suggest that the mast cell-specific proteases may play important roles during parasitic infections, but most of these studies have used young (<10 weeks old) mice, i.e., mice that are still growing and gaining weight, while mature adult (>18 weeks old) mice are rarely used.…”

mentioning

confidence: 99%

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

Peirasmaki

Svärd

et al. 2020

Cells

View full text Add to dashboard Cite

Mast cells have been shown to affect the control of infections with the protozoan parasite Giardia intestinalis. Recently, we demonstrated that Giardia excretory-secretory proteins inhibited the activity of the connective tissue mast cell-specific protease chymase. To study the potential role of the chymase mouse mast cell protease (mMCP)-4 during infections with Giardia, mMCP-4 +/+ and mMCP-4 −/− littermate mice were gavage-infected with G. intestinalis trophozoites of the human assemblage B isolate GS. No significant changes in weight gain was observed in infected young (≈10 weeks old) mMCP-4 −/− and mMCP-4 +/+ littermate mice. In contrast, infections of mature adult mice (>18 weeks old) caused significant weight loss as compared to uninfected control mice. We detected a more rapid weight loss in mMCP-4 −/− mice as compared to littermate mMCP-4 +/+ mice. Submucosal mast cell and granulocyte counts in jejunum increased in the infected adult mMCP-4 −/− and mMCP-4 +/+ mice. This increase was correlated with an augmented intestinal trypsin-like and chymotrypsin-like activity, but the myeloperoxidase activity was constant. Infected mice showed a significantly lower intestinal neutrophil elastase (NE) activity, and in vitro, soluble Giardia proteins inhibited human recombinant NE. Serum levels of IL-6 were significantly increased eight and 13 days post infection (dpi), while intestinal IL-6 levels showed a trend to significant increase 8 dpi. Strikingly, the lack of mMCP-4 resulted in significantly less intestinal transcriptional upregulation of IL-6, TNF-α, IL-25, CXCL2, IL-2, IL-4, IL-5, and IL-10 in the Giardia-infected mature adult mice, suggesting that chymase may play a regulatory role in intestinal cytokine responses.Cells 2020, 9, 925 2 of 19 infections, including infections with G. intestinalis [9][10][11]. However, there is little insight into how Giardia spp. cause disease; they are not invasive and secrete no known toxins [12]. Recent research suggests that G. intestinalis can secrete a large number of immunomodulatory proteins, possibly regulating host immune responses [13][14][15][16]. However, the mechanisms on how interactions between the host and Giardia either lead to parasite clearance or to disease remain to be understood.Recent studies have shown the importance of different immune cells in giardiasis, where both innate and adaptive immunity seem to play significant roles [17][18][19]. Accumulated data suggest that there is a mixed Th1/Th2/Th17 response during giardiasis [19,20]. When G. intestinalis attach to the microvillus brush border of intestinal epithelial cells (IECs) there is a production of chemokines and cytokines that will attract immune cells to the intestinal submucosa [20][21][22]. However, the effects differ depending on model systems used. In cultured human IECs challenged by G. intestinalis trophozoites (assemblage B, isolate GS), several chemokines were highly up-regulated early-at 1.5 h after challenge [21]. In experimental infections of gerbils with the WB isolate (ATCC 50803)...

show abstract

mentioning

confidence: 99%

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

Peirasmaki

Svärd

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Besides, tryptase activates the expression of PAR-2 by endothelial cells, which could propitiate leukocyte rolling, adhesion, and extravasation (Nystedt et al 1996;Vergnolle 1999;Meyer et al 2005;Cleator et al 2006), also contributing to the inflammatory process in T. cruzi-infected individuals. We have recently demonstrated increased numbers of tryptase-IR mast cells in the esophagus of T. cruzi-infected individuals, indicating that such alteration might be a common feature of digestive pathology of Chagas disease (Martins et al 2014).…”

Section: Discussionmentioning

confidence: 94%

“…Increased numbers of tryptase-IR mast cells have been already described in several diseases of the gastrointestinal tract, such as ulcerative colitis (Stoyanova and Gulubova 2002;Albert et al 2011;Stasikowska-Kanicka et al 2012), Crohn's disease (Raithel et al 2001;Christerson et al 2009;Smyth et al 2013), and chagasic megaesophagus (Martins et al 2014). Those disorders have in common an exacerbated inflammatory process, which could be maintained by high levels of tryptase.…”

Section: Discussionmentioning

confidence: 97%

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

et al. 2015

Self Cite

View full text Add to dashboard Cite

Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

show abstract

“…However, increased numbers of chymase-immunoreactive MCs were only found in the esophagus sections of infected individuals without megaesophagus compared to the control groups. Therefore, patients with megaesophagus had increased levels of tryptase-immunoreactive MCs (14). …”

Section: Mcs In Trypanosoma Spp Infectionmentioning

confidence: 99%

“…It is well known that MCs play an important role in parasitic helminth infections (13). Accumulating evidences have demonstrated that MCs have pivotal roles in parasitic protozoan diseases (14, 15); this has led us to focus on the role of MCs in the immune responses against parasitic infections including Plasmodium spp., Leishmania spp., Trypanosoma spp., and T. gondii . The main function of MCs in the aforementioned protozoa is summarized in Table 1.…”

Section: Introductionmentioning

confidence: 99%

The Roles of Mast Cells in Parasitic Protozoan Infections

Huang

2017

Front. Immunol.

View full text Add to dashboard Cite

Protozoan parasites such as Plasmodium spp., Leishmania spp., Trypanosoma spp., and Toxoplasma gondii are major causes of parasitic diseases in both humans and animals. The immune system plays a critical role against protozoa, but their immune mechanism remains poorly understood. This highlights the need to investigate the function of immune cells involved in the process of parasite infections and the responses of host immune system to parasite infections. Mast cells (MCs) are known to be central players in allergy and anaphylaxis, and it has been demonstrated that MCs have crucial roles in host defense against a number of different pathogens, including parasites. To date, there are many studies that have examined the interaction of helminth-derived antigens and MCs. As one of the major effector cells, MCs also play an important role in the immune response against some parasitic protozoa, but their role in protozoan infections is, however, less well characterized. Herein, we review the current knowledge about the roles of MCs and their mediators during infections involving highly pathogenic protozoa including Plasmodium spp., Leishmania spp., Trypanosoma spp., and T. gondii. We offer a general review of the data from patients and experimental animal models infected with the aforementioned protozoa, which correlate MCs and MC-derived mediators with exacerbated inflammation and disease progression as well as protection against the parasitic infections in different circumstances. This review updates our current understanding of the roles of MCs during parasitic protozoan infections, and the participation of MCs in parasitic protozoan infections could be of a potential therapeutic target.

show abstract

Neuroimmunopathology of Trypanosoma cruzi-induced megaoesophagus: Is there a role for mast cell proteases?

Cited by 10 publications

References 23 publications

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

The Roles of Mast Cells in Parasitic Protozoan Infections

Contact Info

Product

Resources

About