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. 2021 Feb 5;79(3):ftab013. doi: 10.1093/femspd/ftab013

Table 2.

Fungal virulence factors and known evasion targets within the mammalian and gallerian immune system. Key: # = findings in Galleria with non-human fungal pathogens (i.e. entomopathogenic fungi); * = findings in non-Galleria lepidopteran species; ROS = reactive oxygen species. 'Not specified' indicates that the factor plays a role in virulence within Galleria; however, the mechanism of action or target within the immune system is not known. Overall, this paints a picture that fungal virulence factors have many overlapping properties during infections of Galleria, although there is a lack of many in-depth mechanistic studies.

Virulence factor Evasion from component of the mammalian immune system? Evasion from component of the gallerian immune system? References
Rodlet layer C-type lectins, opsonization, phagocytosis, NETosis Yes (#), not specified (Altincicek et al. 2008; Aimanianda et al. 2009; Dagenais et al. 2010; Zhang et al. 2011; Branzk and Papayannopoulos 2013; Trevijano-Contador et al. 2015; Shu et al. 2016)
Mycotoxins (gliotoxin and fumagillin) NF-κB signaling (gliotoxin), oxidative bursts, phagocytosis Oxidative bursts, phagocytosis (fumagillin only) (Williams et al. 1986; Shah and Larsen 1991; Wiesner and Götz 1993; Pahl et al. 1996; Shah et al. 1998; Yoshida, Abe and Tsunawaki 2000; Tsunawaki et al. 2004; Coméra et al. 2007; Orciuolo et al. 2007; Bruns et al. 2010; Sakamoto et al. 2015; Vij et al. 2020)
Capsule/GXM C-type lectins, Toll-like receptors, complement system, cytokine release, oxidative bursts, opsonization, phagocytosis, phagolysosomal degradation (pH buffering), NETosis Phagocytosis, oxidative bursts, possibly other interactions (Bull 1970; Bulmer and Tacker 1975; Small and Mitchell 1989; Vecchiarelli et al. 1995; Kozel et al. 1996; Bland and De Lucca 1998; Vecchiarelli 2000; Shoham et al. 2001; Zaragoza, Taborda and Casadevall 2003; Monari et al. 2005; van Asbeck et al. 2008; Okagaki et al. 2010; Zaragoza et al. 2010; García-Rodas et al. 2011; Crabtree et al. 2012; Okagaki and Nielsen 2012; Rossoni et al. 2013; Lev et al. 2014; Rocha et al. 2015; Huang et al. 2018; Casadevall et al. 2019)
Titan cells Phagocytosis Phagocytosis (Small and Mitchell 1989; Kozel et al. 1996; Zaragoza, Taborda and Casadevall 2003; García-Rodas et al. 2011; Okagaki and Nielsen 2012)
Superoxide dismutase Oxidative bursts/ROS Yes (#), likely oxidative bursts/ROS (Reeves et al. 2004; Renwick et al. 2007; Fallon, Reeves and Kavanagh 2010; Fallon, Reeves and Kavanagh 2011)
Catalase Oxidative bursts/ROS Yes*, likely oxidative bursts/ROS (Wysong et al. 1998; Cox et al. 2003; Nakagawa, Kanbe and Mizuguchi 2003; Cuéllar-Cruz et al. 2008; Xie et al. 2010; Li et al. 2015; Broxton and Culotta 2016; Román et al. 2016)
Glutathione Oxidative bursts/ROS Yes, likely oxidative bursts/ROS (Paris et al. 2003; Giles et al. 2006; Wang et al. 2013)
Melanin Oxidative bursts/ROS, antimicrobial peptides, phagocytosis Maybe, conflicting findings but melanin seems to activate the immune system (Kuo and Alexander 1967; Bull 1970; Jacobson and Tinnell 1993; Williamson 1994; Wang, Aisen and Casadevall 1995; Salas et al. 1996; Jahn et al. 1997; Doering et al. 1999; Romero-Martinez et al. 2000; Gómez et al. 2001; Rosas and Casadevall 2001; Nosanchuk et al. 2002; Youngchim et al. 2004; Cunha et al. 2005; Morris-Jones et al. 2005; da Silva et al. 2006; Missall et al. 2006; Jackson, Higgins and Lin 2009; Yadav et al. 2011; Chantasingh et al. 2013; Eisenman et al. 2014; Firacative, Duan and Meyer 2014; Tillmann et al. 2015; Liu et al. 2019; Smith and Casadevall 2019; de Sousa et al. 2020)
Secreted proteases Complement system, opsonization, phagocytosis, antimicrobial peptides, nutrient acquisition Phagocytosis, antimicrobial peptides and non-specified virulence (Hube et al. 1997; Naglik et al. 2004; Gropp et al. 2009; Meiller et al. 2009; Behnsen et al. 2010; Rambach et al. 2010; Sabiiti et al. 2014; Rapala-Kozik et al. 2015; Stappers et al. 2018; Frazão S de et al. 2020)
Acid phosphases Phagolysosomal degradation (nutrient acquisition) Phagolysosomal degradation (nutrient acquisition) (Gago et al. 2014)
Urease/ammonia Phagolysosomal degradation (pH buffering, inhibition of lysosomal fusion) (Gordon, D'Arcy Hart and Young 1980; Cox et al. 2000; Fernández-Arenas et al. 2009; Vylkova et al. 2011; Bain et al. 2014; Vylkova and Lorenz 2014; Rai et al. 2015)
Efflux pumps Antimicrobial peptides—Flu1, phagosomal degradation—Afr1 (inhibition of lysosomal fusion) (Leon-Rodriguez et al. 2018; Ali et al. 2020)
Non-lytic exocytosis and dragotcytosis Phagosomal degradation Phagosomal degradation (non-lytic exocytosis only) (Gordon, D'Arcy Hart and Young 1980; Facchetti et al. 1999; Alvarez and Casadevall 2006; Ma et al. 2006; Mirbod-Donovan et al. 2006; Nicola et al. 2011; Feder et al. 2015; Fu et al. 2018; Seoane and May 2020)
Antiphagocytic protein (APP1) Phagocytosis, complement Yes, not specified (Puccia et al. 2011; Bouklas et al. 2017; Orner et al. 2019)
Morphological switching and cell wall changes C-type lectins (α-glucans, β-glucans), phagocytosis (conidia), phagosomal degradation (inhibition of lysosomal fusion) C-type lectins (α-glucans), phagocytosis (conidia) (Braun and Calderone 1978; Gopal, Shepherd and Sullivan 1984; Medoff et al. 1986; Latgé 1999; Torosantucci, Chiani and Cassone 2000; Netea et al. 2003; Gantner, Simmons and Underhill 2005; van der Graaf et al. 2005; Marion et al. 2006; Renwick et al. 2006; Sanguinetti et al. 2006; Chai et al. 2011; Edwards, Alore and Rappleye 2011; Mora-Montes et al. 2011; Lewis et al. 2012; Lowman et al. 2014)
Filamentation/hyphal growth Toll-like receptors, phagocytosis, phagosomal degradation (inhibition of lysosomal fusion, escape), physical barriers (epithelium/endothelium) Yes, not specified (Lo et al. 1997; Weide and Ernst 1999; Felk et al. 2002; Wasylnka and Moore 2003; Lorenz, Bender and Fink 2004; Sanguinetti et al. 2006; Ghosh et al. 2009; Fuchs et al. 2010; García-Rodas et al. 2011; Seider et al. 2011; Bain et al. 2012; Rai et al. 2015; Westman et al. 2018; Dragotakes, Fu and Casadevall 2019; Seidel et al. 2020)
Biofilms Physical barriers (epithelium/endothelium), oxidative bursts, phagocytosis, antimicrobial peptides Yes, not specified (Kuhn et al. 2002; Martinez and Casadevall 2005, 2006a,b, 2007; Mendes et al. 2007; Ben-Ami et al. 2008; Seidler, Salvenmoser and Müller 2008; Xu et al. 2016; Aslanyan et al. 2017; Kong et al. 2017; Sherry et al. 2017; Romera et al. 2019)
Age Oxidative bursts, phagocytosis Yes, not specified (Rappleye, Eissenberg and Goldman 2007; Puccia et al. 2011; Thomaz et al. 2013; Bouklas et al. 2017; Orner et al. 2019)
Calcineurin Temperature barriers/resistance, fever Temperature barriers/resistance (Morschhäuser et al. 1997; Schaller et al. 1999b; Chen et al. 2012; Casadevall, Kontoyiannis and Robert 2019; Marcos-Zambrano and LJ 2020)