Increased tumour necrosis factor-α production, higher mannose receptor activity and ability to killCandidaby concanavalin-A-activated macrophages

Abstract

In a previous study, our group verified that mice pretreated with concanavalin-A (Con-A) produced more tumour necrosis factor (TNF)-alpha and presented greater Candida clearance from the peritoneal cavity, liver and spleen, which yielded a higher survival rate than control animals. In this work, the hypothesis that macrophages were of crucial importance in overcoming the infection was tested. Thus, peritoneal macrophages from mice pretreated for 3 days with Con-A or phosphate-buffered saline (PBS) were coincubated with CR1, CR15 and 577 isolates of Candida albicans for 0.5, 1 and 2 h. The ability of Con-activated macrophages to produce TNF-alpha, ingest via mannose receptors and kill all the isolates was significantly greater compared with PBS-treated macrophages, and activated macrophages exhibited a lower incidence of apoptosis, verified by binding to annexin V-fluorescein isothiocyanate. The transition of yeast cells to filamentous forms during coincubation for 2 h with control macrophages was about 73-80%, whereas in the presence of Con-A-activated macrophages, it was 35-40%. Our results suggest that a greater clearance of C. albicans infection through treatment with Con-A is probably due to the activation of macrophages, which produce more TNF-alpha, express more mannose receptors and are better endowed to kill ingested C. albicans.

Artin M enhances TNF-α production and phagocytosis of Candida albicans mediated by dectin-1 and mannose receptors

“…These samples were also plated on Sabouraud dextrose agar and the procedure showed a significant reduction in CFU, establishing a correlation with the production of TNF-α. Our group demonstrated a direct correlation between increased TNF-α production and reduced fungal burden in macrophages from mice pretreated with concanavalin-A [12]; moreover, double knockout mice for TNF-α and lymphotoxin-α showed increased susceptibility to disseminated candidiasis [25], correlating with our results.…”

“…2C). This finding suggests that internalization of Candida is necessary to trigger signaling via dectin-1 receptors, although other receptors such as mannose, Toll-like 2 and Toll-like 4 could participate in the increase in TNF-α levels [10][11][12].…”

“…TLR2 deficient mice experimentally infected in vivo showed a significantly reduced survival rate and presented impaired production of TNF-α and IFN-γ [11]. In a previous work, our group demonstrated that increased expression and activity of mannose receptors by pretreatment with concanavalin-A favored TNF-α production and a higher capacity to kill C. albicans [12].…”

Vaginal Epithelial Cell-Derived S100 Alarmins Induced by Candida albicans via Pattern Recognition Receptor Interactions Are Sufficient but Not Necessary for the Acute Neutrophil Response during Experimental Vaginal Candidiasis

“…Indeed, Toll-like receptor 4 (TLR4) expressed on phagocytes as well as vaginal epithelial cells plays a significant role in proinflammatory responses to C. albicans (27,28). In addition, TLR2, SIGNR1, dectin-1, and mannose receptor (MR) are also known to be involved in recognition of C. albicans (29)(30)(31)(32)(33)(34)(35)(36)(37). The purposes of the present study were to further evaluate the biological role of S100A8 alarmin for the vaginal PMN response in the established mouse model and to identify PRRs involved in the induction of the alarmin response.…”

Interações entre Candida albicans e hospedeiro

“…A co-relação do CR3 e receptores da porção Fc de imunoglobulinas, na fagocitose de hifa ou na opsonização de levedura, resultam na produção de IL-4 e/ou IL-10, aumentando a regulação de moléculas co-estimulatórias e MHC-II, assim como a ativação de células TH2/Treg (ROMANI; BISTONI; PUCCETTI, 2002). Candida albicans que induzem apoptose quando opsonizadas com soro fresco de camundongo são ingeridas via CR3 aumentando a freqüência de macrófagos apoptóticos e diminuindo significativamente a produção de TNF-α comparado a ingestão via receptores de manose (GERALDINO et al, 2010).…”