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

Abstract

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)-1β 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.

Sporotrichosis Outbreak Due to Sporothrix brasiliensis in Domestic Cats in Magallanes, Chile: A One-Health-Approach Study

“…Some reports recommend itraconazole associated with potassium iodide, for deeper lesions located in the nasal region, which invade the cartilage beneath [ 58 , 90 ]. The general condition of the cat, the presence or absence of respiratory signs, as well as the number, extension, and location of the lesions are factors that can influence the prognosis [ 9 , 54 , 86 ].…”

“…Sporothrix spp. is a dimorphic fungus, which, in its saprophytic phase, develops a filamentous form, mainly in soils rich in organic matter, at 25 °C; while at 37 °C, in the host tissues, it remains as yeast, generating infection; both phases of the fungus are culturable in the laboratory [ 8 , 9 , 10 , 11 , 12 ].…”

“…The development of the disease is related to predisposing factors such as exposure to the infectious agent, the depth of the wound, and the immune response the host [ 9 , 53 , 54 ]. The incubation period varies from 13 days to 3 months, mainly affecting the skin and lymph nodes adjacent to the lesion.…”

Editorial: Interactions of Pentraxins and Complement in Infection, Inflammation, and Cancer

“…Using two pathogenic Sporothrix species, Sporothrix schenckii ( S. schenckii ) and Sporothrix brasiliensis ( S. brasiliensis ), as model of infections, Neves et al. identified a unique PAMP on the cell wall of Sporothrix species involved in complement-dependent immune responses ( 13 ). They found that cell wall peptidorhamnomannan is responsible for mediating phagocytosis and inflammatory cytokine expression against challenge of Sporothrix species through opsonization and activation of complement receptor 3 (CR3) in a complement-dependent fashion.…”

Explorando as vias de inflamação em infecções fúngicas endêmicas e potenciais novas estratégias de tratamento

“…Recently, peptidorhamnomannan (PRM) has been described for S. brasiliensis and S. schenckii as the major cell wall component present on the outer layer of both fungi and responsible for the recognition of the fungi by human macrophages via CR3. The same authors also observed cooperation between CR3 and TLR4 in IL-1 induction and secretion of pentraxin-3(22).The Th1 and Th17 response are crucial for host protection during histoplasmosis and sporotrichosis (4,16). Differentiation of T CD4 + cells into the Th1 subset requires IL-12 and IFN-, while Th17 subset requires TGF--6, IL-21 and IL-23, which are cytokines produced after CLR or TLR activation (14).…”