Matrix metalloproteinases contribute to the regulation of chemokine expression and pulmonary inflammation in <i>Cryptococcus</i> infection

Supasorn, Oratai; Sringkarin, Nuntarat; Srimanote, Potjanee; Angkasekwinai, Pornpimon

doi:10.1111/cei.12725

Cited by 22 publications

(14 citation statements)

References 38 publications

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“…Since the increase of MMP12 mRNA levels in response to C . neoformans infection has been demonstrated previously [27], we sought to further explore the potential function of OC-STAMP and MMP12 in pulmonary infection by C . neoformans .…”

Section: Resultsmentioning

confidence: 99%

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates

Li¹,

Li²,

Sun³

et al. 2019

PLoS Negl Trop Dis

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Pathogens and hosts require rapid modulation of virulence and defense mechanisms at the infection axis, but monitoring such modulations is challenging. In studying the human fungal pathogen Cryptococcus neoformans , mouse and rabbit infection models are often employed to shed light on the disease mechanisms but that may not be clinically relevant. In this study, we developed an animal infection model using the non-human primate cynomolgus monkey Macaca fascicularis . In addition, we systematically profiled and compared transcriptional responses between the infected mice and the cynomolgus monkey, using simultaneous or dual RNA next-generation sequencing. We demonstrated that there are shared but distinct transcriptional profiles between the two models following C . neoformans infection. Specifically, genes involved in immune and inflammatory responses are all upregulated. Osteoclastogenesis and insulin signaling are also significantly co-regulated in both models and disrupting an osteoclastogenesis-associated gene (OC-STAMP) or the insulin-signaling process significantly altered the host tolerance to C . neoformans . Moreover, C . neoformans was shown to activate metal sequestration, dampen the sugar metabolism, and control cell morphology during infection. Taking together, we described the development of a non-human primate model of cryptococcosis that allowed us to perform an in-depth analysis and comparison of transcriptome profiles during infections of two animal models and conceptually identify host genes important in disease responses. This study provides new insights in understanding fungal pathogenesis mechanisms that potentially facilitate the identification of novel drug targets for the treatment of cryptococcal infection.

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Section: Resultsmentioning

confidence: 99%

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates

Li¹,

Li²,

Sun³

et al. 2019

PLoS Negl Trop Dis

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show abstract

“…Thus, MMPs act as extracellular proteases that modulate, for example, the immune response in pulmonary inflammatory processes. In the case of Cryptococcus infection the MMP-12 levels are strongly correlated with the expression of the macrophage- and neutrophil-attracting chemokine CCL2 mRNA [ 96 ]. It is noteworthy that TiO 2 NPs induce the expression of elastase-induced MMP-12 mRNA in the lung [ 97 ] and in murine macrophages [ 98 ].…”

Section: Extracellular Matrixmentioning

confidence: 99%

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

et al. 2017

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Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

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“…After incubating for 2 hours, nonadherent cells were removed and alveolar macrophages (adherent cells) were washed and harvested with a rubber scraper for further RNA extraction. Cell viability was determined using trypan blue exclusion and purity was analyzed with CD11b staining by FACS analysis [18].…”

Section: Alveolar Macrophage Isolationmentioning

confidence: 99%

Cryptococcus neoformans and Cryptococcus gattii clinical isolates from Thailand display diverse phenotypic interactions with macrophages

et al. 2018

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Cryptococcus-macrophage interaction is crucial in the development of cryptococcocal diseases. C. neoformans and C. gattii are major pathogenic species that occupy different niches and cause different clinical manifestations. However, the differences of macrophage interaction among these species in affecting different disease outcomes and immune responses have not been clearly addressed. Here, we examined the macrophage uptake rates, intracellular loads and intracellular proliferation rates of C. neoformans and C. gattii clinical isolates from Thailand and analyzed the effect of those interactions on fungal burdens and host immune responses. C. neoformans isolates showed a higher phagocytosis rate but lower intracellular proliferation rate than C. gattii. Indeed, the high intracellular proliferation rate of C. gattii isolates did not influence the fungal burdens in lungs and brains of infected mice, whereas infection with high-uptake C. neoformans isolates resulted in significantly higher brain burdens that associated with reduced survival rate. Interestingly, alveolar macrophages of mice infected with high-uptake C. neoformans isolates showed distinct patterns of alternatively activated macrophage (M2) gene expressions with higher Arg1, Fizz1, Il13 and lower Nos2, Ifng, Il6, Tnfa, Mcp1, csf2 and Ip10 transcripts. Corresponding to this finding, infection with high-uptake C. neoformans resulted in enhanced arginase enzyme activity, elevated IL-4 and IL-13 and lowered IL-17 in the bronchoalveolar lavage. Thus, our data suggest that the macrophage interaction with C. neoformans and C. gattii may affect different disease outcomes and the high phagocytosis rates of C. neoformans influence the induction of type-2 immune responses that support fungal dissemination and disease progression.Abbreviation: Arg1: Arginase 1; BAL: Bronchoalveolar lavage; CCL17: Chemokine (C-C motif) ligand 17; CNS: Central nervous system; CSF: Cerebrospinal fluid; Csf2: Colony-stimulating factor 2; Fizz1: Found in inflammatory zone 1; HIV: Human immunodeficiency virus; ICL: Intracellular cryptococcal load; Ifng: Interferon gamma; Ip10: IFN-g-inducible protein 10; IPR: Intracellular proliferation rate; Mcp1: Monocyte chemoattractant protein 1; Nos2: Nitric oxide synthase 2; PBS: Phosphate-Buffered Saline; Th: T helper cell; Tnfa: Tumor necrosis factor alpha.

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Matrix metalloproteinases contribute to the regulation of chemokine expression and pulmonary inflammation in Cryptococcus infection

Cited by 22 publications

References 38 publications

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

Cryptococcus neoformans and Cryptococcus gattii clinical isolates from Thailand display diverse phenotypic interactions with macrophages

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