Abstract
Since its first description in 2002 [1], the inflammasome has been implicated in the mechanisms underlying a growing number of infectious, autoimmune, and metabolic diseases [2]. Regarding infectious processes, several studies have shown the involvement of this critical component of innate immunity in the outcome of infection with nearly every class of microbe, including fungi [3]. Innate immunity is the frontline of defense against infection and relies on the ability of its main players (phagocytes and epithelial barriers) to detect conserved components of microbes or pathogen-associated molecular patterns (PAMPs). In fungi, the carbohydrate polymers of the cell wall, such as chitin, β-glucan, and mannan are the major PAMPs recognized by the host’s innate immune cells; this recognition occurs via germline-encoded receptors termed pattern recognition receptors (PRRs) [4]. In addition to PAMPs, endogenous molecules associated with damaged host cells, or damage-associated molecular patterns (DAMPs), are released during tissue injury and activate PRRs. This innate detection system includes the Toll-like receptors (TLRs), C-type lectin receptors (CLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and AIM2-like receptors (ALRs). Although the main fungal- recognition PRRs (CLRs and TLRs) are bound to the cytoplasmic membrane of innate immune cells [4], fungal sensing by PRRs located in the cytosol, such as the NLRs and ALRs, is becoming increasingly evident. A number of NLRs and ALRs can assemble into the inflammasome, a multiprotein complex consisted of PRRs such as NLRP3 (NLR family, pyrin domain-containing 3), NLRC4, or AIM2, adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (CARD), and procaspase-1 [3]. Upon formation of the complex, procaspase-1 is cleaved into an active cysteine protease, which further cleaves the proinflammatory cytokines IL-1β and IL-18 into their mature forms, followed by unconventional secretion. IL-1β and IL-18 mediate several innate antimicrobial responses and are critical to direct adaptive Th17/Th1 cellular responses [5]. In addition, inflammasome activation causes pyroptosis, a lytic inflammatory form of cell death [2,5].
Highlights
This finding led to several experiments demonstrating a NOD-like receptors (NLRs)-independent dectin-1/Syk-dependent inflammasome activation route, with the assembly of the CBM scaffold and processing of IL-1β mediated by recruitment of MALT-1/caspase-8 and ASC into this complex
Considering that bacterial RNA and DNA are sensed by NLRP3 [34], it is possible that NLRP3 and AIM2 both recognize a common nucleic acid composition of A. fumigatus, prompting the formation of a cooperative inflammasome
Our group demonstrated that the presence of the IL-1 receptor (IL-1R)-dependent signaling, and NLRP3 is required to control the intracellular growth of P. brasiliensis within macrophages [15]
Summary
Citation: Tavares AH, Bürgel PH, Bocca AL (2015) Turning Up the Heat: Inflammasome Activation by Fungal Pathogens. PLoS Pathog 11(7): e1004948. doi:10.1371/journal.ppat.1004948 Funding: This work was funded by CNPq and CAPES. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
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