The aspergillus fumigatus mucin msba regulates the cell wall integrity pathway and controls recognition of the fungus by the immune system
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Resumo
Aspergillus fumigatus is a filamentous fungus which causes invasive pulmonary aspergillosis in immunocompromised individuals. In fungi, cell signaling and cell wall plasticity are crucial for maintaining physiologic processes. In this context, Msb2 is an important signaling mucin responsible for activation of a variety of mitogen-activated protein kinase (MAPK)-dependent signaling pathways that regulate cell growth in several organisms, such as the cell wall integrity (CWI) pathway. Here, we aimed to characterize the MSB2 homologue in A. fumigatus. Our results showed that MsbA plays a role in the vegetative and reproductive development of the fungus, in stress adaptation, and in resistance to antifungal drugs by modulating the CWI pathway gene expression. Importantly, cell wall composition is also responsible for activation of diverse receptors of the host immune system, thus leading to a proper immune response. In a model of acute Aspergillus pulmonary infection, results demonstrate that the ΔmsbA mutant strain induced less inflammation with diminished cell influx into the lungs and lower cytokine production, culminating in increased lethality rate. These results characterize for the first time the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis and an important regulator of virulence.
Abstract
Assunto
Biologia, Aspergillus fumigatus, Paredes celular fúngica
Palavras-chave
Aspergillus fumigatus, Cell wall integrity, Immune response, MSB2, Mucin, Virulence
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https://journals.asm.org/doi/10.1128/mSphere.00350-19