Macrophage Mediated Immunomodulation During Cryptococcus Pulmonary Infection

Wang, Yan; Pawar, Siddhi; Dutta, Orchi; Wang, Keyi; Rivera, Amariliz; Xue, Chaoyang

doi:10.3389/fcimb.2022.859049

Cited by 21 publications

(13 citation statements)

References 163 publications

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“…As an initial step to understand BRI MoA, we screened a C. neoformans H99 transcription factor (TF) null mutant library 75 for susceptibility to BRI. To do this we grew 322 signature-tagged gene deletion strains, corresponding to 155 putative TF genes, at 30 o C on liquid RPMI+BRI (1.25 µM) and then plated them on fresh solid YPD.…”

Section: Resultsmentioning

confidence: 99%

Brilacidin, a novel antifungal agent againstCryptococcus neoformans

Diehl,

Pinzan,

de Castro

et al. 2024

Preprint

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Cryptococcus neoformanscauses cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug againstC. neoformans. BRI is able to affect the organization of the cell membrane, increasing fungal cell permeability. We also investigated the effects of BRI against the model systemSaccharomyces cerevisiaeby analyzing libraries of mutants grown in the presence of BRI. InS. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reducesC. neoformanssurvival inside macrophages and partially clearsC. neoformanslung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action againstC. neoformans. BRI+CAS affects endocytic movement, calcineurin, and mitogen activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.

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Section: Resultsmentioning

confidence: 99%

Brilacidin, a novel antifungal agent againstCryptococcus neoformans

Diehl,

Pinzan,

de Castro

et al. 2024

Preprint

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“…In our research, rTcpC treatment profoundly promoted expression of CD163 and CD206 in THP-1 and J774A.1 and stimulated differentiation into M2 macrophages with IL-4, demonstrating that TcpC promotes M2a macrophage polarization, hereby favoring UPEC to escape from the macrophage-mediated inflammatory anti-infection response. The polarization of macrophages is regulated during the infection of some pathogenic microorganisms including Cryptococcus neoformans [ 50 , 51 ], Mycobacterium tuberculosis [ 52 ], Staphylococcus aureus [ 32 ], influenza virus [ 53 ] and SARS-CoV-2 virus [ 54 ]. In addition, some factors have been reported to regulate macrophage polarization, such as RORα, ZIP9, TSC and p190RhoGEF, and inhibit M1 macrophage polarization [ 34 , 55 , 56 , 57 ], while YAP restrains M2 macrophage polarization [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

TcpC Inhibits M1 but Promotes M2 Macrophage Polarization via Regulation of the MAPK/NF-κB and Akt/STAT6 Pathways in Urinary Tract Infection

Fang

et al. 2022

Cells

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TcpC is a multifunctional virulence factor of Uropathogenic Escherichia coli (UPEC). Macrophages can differentiate into two different subsets M1 and M2 that play distinct roles in anti-infection immunity. Here, we investigate the influence of TcpC on M1/M2 polarization and the potential mechanisms. Our data showed that M1 markers CD86 and iNOS were significantly inhibited, while the M2 markers CD163, CD206 and Arg-1 were enhanced in macrophages in kidneys from the TcpC-secreting wild-type CFT073 (CFT073wt)-infected pyelonephritis mouse model, compared with those in macrophages in kidneys from TcpC knockout CFT073 mutant (CFT073Δtcpc)-infected mice. CFT073wt or recombinant TcpC (rTcpC) treatment inhibits LPS + IFN-γ-induced CD80, CD86, TNF-α and iNOS expression, but promotes IL-4-induced CD163, CD206, Arg-1 and IL-10 expression in both human and mouse macrophage cell lines THP-1 and J774A.1. Moreover, rTcpC significantly attenuated LPS + IFN-γ-induced phosphorylation of p38, ERK, p50 and p65 but enhanced IL-4-induced phosphorylation of Akt and STAT6. These data suggest that TcpC inhibits M1 but promotes M2 macrophage polarization by down-regulation of p38, ERK/NF-κB and up-regulation of the Akt/STAT6 signaling pathway, respectively. Our findings not only illuminate the regulatory effects of TcpC on macrophage M1/M2 polarization and its related signaling pathways, but also provide a novel mechanism underlying TcpC-mediated immune evasion of macrophage-mediated innate immunity.

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“…The close interaction of Cryptococcus and phagocytes in the host dictates why it is defined as a facultative intracellular pathogen ( Wang et al., 2022 ). Phagocytes provide a protective niche for Cryptococcus to replicate, proliferate, and even be dormant when the host immunity is overexpressed.…”

Section: Fungal Structure and Corresponding Immune Escape Mechanisms ...mentioning

confidence: 99%

Cryptococcus escapes host immunity: What do we know?

Yang

Huang

Zhou

et al. 2022

Front. Cell. Infect. Microbiol.

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Cryptococcus is an invasive fungus that seriously endangers human life and health, with a complex and well-established immune-escaping mechanism that interferes with the function of the host immune system. Cryptococcus can attenuate the host’s correct recognition of the fungal antigen and escape the immune response mediated by host phagocytes, innate lymphoid cells, T lymphocytes, B lymphocytes with antibodies, and peripheral cytokines. In addition, the capsule, melanin, dormancy, Titan cells, biofilm, and other related structures of Cryptococcus are also involved in the process of escaping the host’s immunity, as well as enhancing the ability of Cryptococcus to infect the host.

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Macrophage Mediated Immunomodulation During Cryptococcus Pulmonary Infection

Cited by 21 publications

References 163 publications

Brilacidin, a novel antifungal agent againstCryptococcus neoformans

Brilacidin, a novel antifungal agent againstCryptococcus neoformans

TcpC Inhibits M1 but Promotes M2 Macrophage Polarization via Regulation of the MAPK/NF-κB and Akt/STAT6 Pathways in Urinary Tract Infection

Cryptococcus escapes host immunity: What do we know?

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