Common virulence factors between Histoplasma and Paracoccidioides: Recognition of Hsp60 and Enolase by CR3 and plasmin receptors in host cells.

Over the last two decades, the incidence of Invasive Fungal Infections (IFIs) globally has risen, posing a considerable challenge despite available antifungal therapies. Addressing this, the World Health Organization (WHO) prioritized research on specific fungi, notably Histoplasma spp. and Paracoccidioides spp. These dimorphic fungi have a mycelial life cycle in soil and a yeast phase associated with tissues of mammalian hosts. Inhalation of conidia and mycelial fragments initiates the infection, crucially transforming into the yeast form within the host, influenced by factors like temperature, host immunity, and hormonal status. Survival and multiplication within alveolar macrophages are crucial for disease progression, where innate immune responses play a pivotal role in overcoming physical barriers. The transition to pathogenic yeast, triggered by increased temperature, involves yeast phase-specific gene expression, closely linked to infection establishment and pathogenicity. Cell adhesion mechanisms during host-pathogen interactions are intricately linked to fungal virulence, which is critical for tissue colonization and disease development. Yeast replication within macrophages leads to their rupture, aiding pathogen dissemination. Immune cells, especially macrophages, dendritic cells, and neutrophils, are key players during infection control, with macrophages crucial for defense, tissue integrity, and pathogen elimination. Recognition of common virulence molecules such as heat- shock protein-60 (Hsp60) and enolase by pattern recognition receptors (PRRs), mainly via the complement receptor 3 (CR3) and plasmin receptor pathways, respectively, could be pivotal in host-pathogen interactions for Histoplasma spp. and Paracoccidioides spp., influencing adhesion, phagocytosis, and inflammatory regulation. This review provides a comprehensive overview of the dynamic of these two IFIs between host and pathogen. Further research into these fungi's virulence factors promises insights into pathogenic mechanisms, potentially guiding the development of effective treatment strategies.

Aminopeptidase N/CD13 Crosslinking Promotes the Activation and Membrane Expression of Integrin CD11b/CD18.

The ß2 integrin CD11b/CD18, also known as complement receptor 3 (CR3), and the moonlighting protein aminopeptidase N (CD13), are two myeloid immune receptors with overlapping activities: adhesion, migration, phagocytosis of opsonized particles, and respiratory burst induction. Given their common functions, shared physical location, and the fact that some receptors can activate a selection of integrins, we hypothesized that CD13 could induce CR3 activation through an inside-out signaling mechanism and possibly have an influence on its membrane expression. We revealed that crosslinking CD13 on the surface of human macrophages not only activates CR3 but also influences its membrane expression. Both phenomena are affected by inhibitors of Src, PLCγ, Syk, and actin polymerization. Additionally, after only 10 min at 37 °C, cells with crosslinked CD13 start secreting pro-inflammatory cytokines like interferons type 1 and 2, IL-12p70, and IL-17a. We integrated our data with a bioinformatic analysis to confirm the connection between these receptors and to suggest the signaling cascade linking them. Our findings expand the list of features of CD13 by adding the activation of a different receptor via inside-out signaling. This opens the possibility of studying the joint contribution of CD13 and CR3 in contexts where either receptor has a recognized role, such as the progression of some leukemias.

Influence of Pre-Milling of Cr3C2-25 NiCr Spray Powder on the Fatigue Life of HVOF-Sprayed Coating on ASTM A516 Steel Substrate.

The aim of the present investigation is to evaluate the influence of the powder size of Cr3C2-25NiCr spraying powder on the fatigue behavior of HVOF-sprayed coating on the ASTM A516 steel substrate. Conventional commercial Cr3C2-25NiCr spraying powder was previously treated through high-energy milling. The crystallite sizes of milled powders were measured by X-ray diffraction and transmission electronic microscopy. Three different powder formats of the same Cr3C2-25NiCr composite were subjected to HVOF spraying to produce (i) a Milled-Coating (from high-energy milled spray powder), (ii) an Original-Coating (from conventional commercial spray powder), and (iii) a 50%-50% mixture of both (Milled + Original-Coating). The same spraying conditions were adopted for all the assessed cases. The sprayed coatings were investigated through the Knoop hardness test and SEM-EDS analysis. In addition, 3-point bending fatigue tests were conducted at different stress levels up to 107 cycles. The coating morphology and roughness effects on fatigue behavior were analyzed. The Cr3C2-25NiCr milled coating presented a lower fatigue life above the fatigue limit and a higher fatigue limit than other coatings; this outcome could be attributed to its lower surface roughness and finer grain size microstructure.

Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans.

In this study, the human immune response mechanisms against Sporothrix brasiliensis and Sporothrix schenckii, two causative agents of human and animal sporotrichosis, were investigated. The interaction of S. brasiliensis and S. schenckii with human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis of Sporothrix yeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these two Sporothrix yeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on the Sporothrix yeast surfaces. PRM also showed direct interaction with CD11b, the specific component of the complement receptor-3 (CR3). Furthermore, the blockade of CR3 specifically impacted the interleukin (IL)-1ß secretion by hMDM in response to both S. brasiliensis and S. schenckii, suggesting that the host complement system plays an essential role in the inflammatory immune response against these Sporothrix species. Nevertheless, the structural differences in the PRMs of the two Sporothrix species, as revealed by NMR, were related to the differences observed in the host complement activation pathways. Together, this work reports a new PAMP of the cell surface of pathogenic fungi playing a role through the activation of complement system and via CR3 receptor mediating an inflammatory response to Sporothrix species.

Corrosion Behavior and Galvanic Corrosion Resistance of WC and Cr3C2 Cermet Coatings in Madeira River Water.

Thermally sprayed cermet coatings are adequate solutions to improve cavitation and wear resistance of hydraulic turbines made of stainless steel (SS), especially in rivers with a high sediment load, such as the Madeira River in Brazil. However, some cermets are easily dissolved in river water, leading to premature failure of the coating and costly maintenance. Moreover, galvanic corrosion induced by coupling the cermet to a SS can accelerate the coating dissolution. Therefore, the corrosion resistance of six cermets (WC-12Co, WC-10Ni, WC-10Co-4Cr, Cr3C2-25NiCr, Cr3C2-10NiCr and Cr3C2-10Ni) and the galvanic corrosion resistance of these materials coupled to CA6NM SS were evaluated in a solution that simulated Madeira River water. WC-12Co and WC-10Ni cermets exhibited the highest corrosion rates, 0.077 and 0.068 mm/year, respectively, whereas the Cr content in the WC-10Co-4Cr (0.017 mm/year) and Cr3C2-based coatings (0.005 to 0.007 mm/year) led them to corrode at slower rates. Moreover, the WC-10Co-4Cr and Cr3C2-based cermets exhibited negligible galvanic corrosion current when coupled to the CA6NM SS, making them good options to coat hydraulic turbines. In contrast, WC-12Co and WC-10Ni coatings underwent a more severe galvanic corrosion process, which would drastically reduce the lifespan of these materials as hydraulic turbine coatings.