Effect of ArtinM on Human Blood Cells During Infection With Paracoccidioides brasiliensis

Abstract

Infections caused by fungi are prominent in our environment and can be potentially fatal. paracoccidioidomycosis (PCM), caused by fungi of the Paracoccidioides genus, is the most frequent systemic mycosis in Brazil and the main cause of death among immunocompetent individuals. The antifungal therapy for PCM is usually effective but side effects and relapses are often reported. The latter could be avoided with alternative or complementary therapies aimed at boosting the immune response to combat this pathogen. Recent reports have pointed at the importance of an effective cellular immune response, with the participation of Th1 cells, in the resistance to and control of Paracoccidioides infection. The ArtinM lectin, extracted from jackfruit (Artocarpus heterophyllus) seeds, exhibits immunomodulatory activity against several intracellular pathogens, including Paracoccidioides brasiliensis, by promoting the development of a Th1 immune response. The aim of this work was to characterize the effect of ArtinM on peripheral blood cells of patients with PCM and on those of control individuals infected with fungal yeasts cells in vitro. Our results demonstrate that ArtinM activates human neutrophils in vitro, leading to an increase in cytokine production and CD54 expression. ArtinM activated P. brasiliensis-infected neutrophils from both healthy individuals and patients with PCM. This activation was not dependent on the dectin-1 receptor, because pre-incubation with laminarin, a dectin-1 receptor blocker, did not reverse the activated state of the cells. ArtinM also stimulated human peripheral blood mononuclear cells to secrete pro-inflammatory Th1-related cytokines, which are protective against Paracoccidioides infection. These data support the immunostimulatory action of ArtinM and encourage new studies using the lectin for the immunotherapy of PCM.

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

“…In mice infected with P. brasiliensis, ArtinM stimulated IL-12 production through a mechanism dependent on TLR2/MyD88 signaling [37,38]. ArtinM also stimulates human peripheral blood cells to secrete pro-inflammatory Th1-related cytokines [39]. ArtinM was also effective against Leishmania amazonensis.…”

Involvement of the Dectin-1 Receptor upon the Effector Mechanisms of Human Phagocytic Cells against Paracoccidioides brasiliensis

“…In PCM, many studies have contributed to the understanding of Dectin-1 receptor functions in human phagocytes. Studies that evaluated the participation of the receptor used different protocols, demonstrating results such as receptor participation in fungal recognition, induction of effector mechanisms, and production of cytokines such as TNF- α [4, 6, 7, 9–11, 35–37]. In experimental models of the disease, there are conflicting data showing the participation of the Dectin-1 receptor in susceptibility and in PCM resistance [5, 8, 11, 38–40].…”

Overview of Antifungal Drugs against Paracoccidioidomycosis: How Do We Start, Where Are We, and Where Are We Going?

“…ArtinM, extracted from the seeds of Artocarpus heterophyllus, showed immunomodulatory activity, inducing IL-12 production and Th1-type immune response polarization in rats infected with P. brasiliensis. This last approach resulted in a reduced fungal load [87].…”