Paracoccidioidomycosis Protective Immunity

Abstract

Protective immunity against Paracoccidioides consists of a stepwise activation of numerous effector mechanisms that comprise many cellular and soluble components. At the initial phase of non-specific innate immunity, resistance against Paracoccidioides comes from phagocytic polymorphonuclear neutrophils, natural killer (NK) cells and monocytes, supplemented by soluble factors such as cytokines and complement system components. Invariant receptors (Toll-like receptors (TLRs), Dectins) which are present in cells of the immune system, detect patterns present in Paracoccidioides (but not in the host) informing the hosts cells that there is an infection in progress, and that the acquired immunity must be activated. The role of components involved in the innate immunity of paracoccidioidomycosis is herein presented. Humoral immunity, represented by specific antibodies which control the fungi in the blood and body fluids, and its role in paracoccidioidomycosis (which was previously considered controversial) is also discussed. The protective mechanisms (involving various components) of cellular immunity are also discussed, covering topics such as: lysis by activated macrophages and cytotoxic T lymphocytes, the participation of lytic products, and the role of cytokines secreted by T helper lymphocytes in increasing the efficiency of Paracoccidioides, lysis.

The Role of Dimorphism Regulating Histidine Kinase (Drk1) in the Pathogenic Fungus Paracoccidioides brasiliensis Cell Wall

“…It is known that the participation of the Dectin-1 receptor together with TLR in the recognition pathway of Paracoccidioides spp. triggers the production of several proinflammatory cytokines [88], such as TNFα. This molecule is produced by cells involved in the immune system, including activated macrophages and regulatory T cells, acting as central mediators in inflammation and the regulation of the immune response [89].…”

Epidemiologic, Clinical and Immunological Consequences of Co-Infections during Canine Leishmaniosis

“…Macrophage P. brasiliensis fungicidal activity is enhanced by IFN-γ and TNF-α, and a Th1 response is associated with protection [ 222 ]. The immunoregulatory cytokine IL-10 antagonizes IFN-γ activity and is associated with susceptibility to P. brasiliensis [ 222 ].…”

“…Macrophage P. brasiliensis fungicidal activity is enhanced by IFN-γ and TNF-α, and a Th1 response is associated with protection [ 222 ]. The immunoregulatory cytokine IL-10 antagonizes IFN-γ activity and is associated with susceptibility to P. brasiliensis [ 222 ]. Patients were significantly more likely (OR = 5.8) to have a single nucleotide polymorphism in the IL-10 gene, resulting in enhanced IL-10 expression [ 223 ].…”

Extracellular Vesicles From Paracoccidioides brasiliensis Can Induce the Expression of Fungal Virulence Traits In Vitro and Enhance Infection in Mice

“…PCM is a granulomatous mycosis that affects mainly the lungs ( Martinez, 2017 ). Protection against PCM is provided by Th1-driven pro-inflammatory immune responses initiated by dendritic cells expressing interleukin (IL)-12 ( Gow et al., 2017 ; Burger, 2021 ; Fernández-García and Cuellar-Rodríguez, 2021 ). Active macrophages and neutrophils are detrimental to the prevention of disease progression.…”

“…Interferon γ (IFN-γ) activates macrophages to express tumor necrosis factor-α (TNF-α) that supports granuloma persistence. The production of effector molecules such as reactive oxygen (ROS) and nitrogen (NOS) species of the respiratory burst by the immune cells is a key effector mechanism in fungal clearance ( Gow et al., 2017 ; Burger, 2021 ; Fernández-García and Cuellar-Rodríguez, 2021 ).…”