Paracoccidioides species present distinct fungal adherence to epithelial lung cells and promote different IL-8 secretion levels

Almeida

Suzuki

2020

Sci Rep

Self Cite

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and may be caused by the species Paracoccidioides brasiliensis. In the lungs, this fungus interacts with epithelial cells, activating host cell signalling pathways, resulting in the production of inflammatory mediators. This event may be initiated through the activation of Pattern-Recognition Receptors such as Toll-like Receptors (TLRs). By interacting with cell wall components, TLR2 is frequently related to fungal infections. In this work, we show that, after 24 h post-infection with P. brasiliensis, A549 lung epithelial cells presented higher TLR2 levels, which is important for IL-8 secretion. Besides, integrins may also participate in pathogen recognition by host cells. We verified that P. brasiliensis increased α3 integrin levels in A549 cells after 5 h of infection and promoted interaction between this receptor and TLR2. However, after 24 h, surprisingly, we verified a decrease of α3 integrin levels, which was dependent on direct contact between fungi and epithelial cells. Likewise, we observed that TLR2 is important to downmodulate α3 integrin levels after 24 h of infection. Thus, P. brasiliensis can modulate the host inflammatory response by exploiting host cell receptors and cell signalling pathways.

supporting

confidence: 64%

Section: Tlr2 Expression Levels In Lung Epithelial Cells Infected Witmentioning

confidence: 88%

mentioning

confidence: 99%

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Paracoccidioides brasiliensis downmodulates α3 integrin levels in human lung epithelial cells in a TLR2-dependent manner

Almeida

Suzuki

2020

Sci Rep

Self Cite

“…To date, little is known about the detailed changes that occur in cytokine profiles after TACE. Due to its rarity, the majority of previous studies have focused on individual cytokines, and prior to the present study, few studies have explored changes in serum cytokines, signaling pathways and disease prognosis based on microarray data (18)(19)(20)(21)(22). The general focus of the present study was to identify differences in the cytokine expression profiles of patients with HCC undergoing TACE with a specific interest in identifying significantly changed biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.…”

Section: Time-series Clustering Of Cytokine Expression After Transartmentioning

confidence: 99%

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2019

Cytokines play an important role in the development of tumors. The purpose of the present study was to evaluate the mechanisms and cytokine level changes after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). The Short Time-series Expression Miner (STEM) program was utilized to cluster cytokine expression profiles from the day before TACE to day 21 post-TACE. Based on the identified significant signatures, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Cytokines were serially monitored in 60 evaluable patients to identify the results of the STEM program. Examination of the significant signatures identified 6 significant time-varied expression patterns for 507 cytokines (profiles 16, 18, 28, 41, 42 and 43). GO analysis was enriched in 'cytokine receptor-binding' and 'cytokine receptor activity', and the identified signaling pathways included 'cytokine-cytokine receptor interaction' and the 'JAK-STAT signaling pathway'. Ciliary neurotrophic factor (CNTF) level was increased early after TACE, reaching a peak on day 7 before finally decreasing from day 14 onwards, and was significantly positively correlated with aminotransferase level. Serum levels of pre-TACE IL-10 predicted the local tumor response and overall survival (OS) of the patients, while serum levels of post-TACE IL-1β only indicated the local tumor response of the patient. Overall, the present study identified cytokine time-series expression profiles of patients with HCC undergoing TACE. Early phase increases in CNTF after TACE were associated with post-treatment hepatic injury. IL-1β may reflect an objective response after TACE, while IL-10 may represent a biomarker for OS and the objective response pre-TACE, which may help patients with HCC to benefit from TACE.

“…Oliveira et al [ 88 ] demonstrated that while P. brasiliensis (Pb18 isolate) adhered more to fibronectin than P. lutzii (Pb01 isolate), P. lutzii presented higher adhesion rates to laminin and collagen types I and IV [ 88 ]. Even though these authors verified that the adhesion of these two species to epithelial cells was similar, Almeida et al [ 89 ] demonstrated that P. lutzii (Pb01 isolate) adhesion rates were seven times higher than those of P. brasiliensis (Pb18 isolate) and P. americana (Pb03 isolate) [ 88 , 89 ]. Such differences might be explained by the distinct methods used among the laboratories to analyze fungal adhesion.…”

Section: Paracoccidioidesmentioning

confidence: 99%

Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections

Almeida

et al. 2022

JoF

The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes. This review will focus on the response of respiratory epithelial cells to two human fungal pathogens that cause systemic mycoses: Aspergillus and Paracoccidioides. Some of the host epithelial cell receptors and signaling pathways, in addition to fungal adhesins or other molecules that are responsible for fungal adhesion, invasion, or induction of cytokine secretion will be addressed in this review.