Host Response and Pathogenesis
Temperature plays an important role in the Sporothrix mycelium-yeast transition. The thermal dimorphism is a morphophysiological adaptation to infection of warmblooded hosts. This transition to an invasive phase is a unique characteristic among Ophiostomatales and is shared with phylogenetically distant human pathogens in Onygenales and Eurotiales (Rodrigues et al.
2016b). In members of the environmental Sporothrix clades such as S. chilensis, S. mexicana, and S. pallida, the mycelium-yeast transition occurs poorly, with development of few yeast cells, which can be related to low virulence to mammalians (Rodrigues et al. 2016a).Once Sporothrix comes into contact with the host, it can stimulate or trigger the natural (innate) and acquired (adaptive) defense mechanisms of the host. Immunity to Sporothrix is conferred by neutrophils and monocytes (Davis 1996). The hypothesis that suggests immunity mediated by T cells as a limiting factor in the progression of infection is because sporotrichosis is more severe in athymic mice and AIDS patients (Donabedian et al. 1994; Tachibana et al. 1999).
The host defense mechanisms affect the manifestation and severity of fungal infections, thereby generating different clinical forms of the disease. Isolates from skin lesions activate dendritic cells, thereby inducing Th1 immune response (Uenotsuchi et al. 2006). S. schenckii is capable of inducing a mixed Th1∕Th2 response in experimental sporotrichosis (Uenotsuchi et al. 2006; Maia et al. 2006). Sassa et al. (2009) suggested that the toll-like receptors (TLR4) play an important role in macrophages in S. schenckii experimental infection.
The humoral response involves potent antigens able to elicit immune responses in the host during colonization and tissue invasion. After infection by S. brasiliensis, B lymphocytes of cats produce an IgG-mediated immune response against Sporothrix antigens, similar to the humoral response observed in murines (Fernandes et al.
2013) and human sporotrichosis (Rodrigues et al. 2015c). Significant crossreactivity exists among antigens of S. brasiliensis, S. schenckii, and S. globosa, supporting the hypothesis that the antigens share epitopes highly conserved among the members of the clinical clade. This also suggests that infection in warm-blooded hosts (humans, cats, and rats) is the result of evolutionary convergence among S. brasiliensis, S. schenckii, and S. globosa (Rodrigues et al. 2015b, c).A protein identified as 3-carboxymuconate cyclase (gp60-70) is considered the main antigen expressed by pathogenic Sporothrix species and recognized by circulating IgG antibodies in the serum of hosts (Rodrigues et al. 2015c). This highly polymorphic glycoprotein, with a molecular weight ranging from 60 to 70 kDa (gp60 and gp70, respectively) and an isoelectric point between 4.3 and 4.8, is present in at least six isoforms and glycoforms. The gp60-70 protein is located in the cell wall of Sporothrix (Castro et al. 2013), where it functions as an adhesin for extracellular matrix molecules such as fibronectin and laminin (Teixeira et al. 2009; Nascimento et al. 2008). Note that anti-gp60-70 antibodies reduce adherence of Sporothrix to the host tissue in a concentration-dependent manner. They facilitate yeast opsonization by phagocytes, reducing the fungal load in the host (Ruiz-Baca et al. 2009; Nascimento et al. 2008). Thus, it is suggested that anti-3- carboxymuconate cyclase antibodies are important effectors in the host defense against the establishment and spread of infection. Rodrigues et al. (2015b) demonstrated the presence of anti-gp60-70 antibodies in felines during epizootics by S. brasiliensis. Preimmunization with 3-carboxymuconate cyclase in experimental sporotrichosis has a negative regulatory effect on the Th1 immune response, with a reduction in cytokine levels (Alba-Fierro et al. 2016). Knowledge of the humoral immune response in feline sporotrichosis is essential to the advance of serological diagnostic techniques, to vaccine production, and to improve our understanding of the evolution of the interaction between Sporothrix and its hosts (Rodrigues et al.
2015b).In experimental sporotrichosis, the study of the host-pathogen interaction focuses on pathogenicity and virulence using several species of Sporothrix. The strains most frequently used are BALB/c, C57BL/6, and OF1 mice in subcutaneous or disseminated inoculation models (Castro et al. 2013; Fernandes et al. 2013; Almeida-Paes et al. 2015; Arrillaga-Moncrieff et al. 2009; Della Terra et al. 2017). The amount of inoculum and the morphotype inoculated, i.e., conidium or yeast, vary among research groups. However, a clear difference exists in the infection ability of species belonging to clinical and environmental clades, respectively. Despite methodological divergences, S. brasiliensis is by far the most virulent species of the clinical clade, followed by S. schenckii, S. luriei, and S. globosa (Fernandes et al. 2013; Arrillaga-Moncrieff et al. 2009; Fernandez-Silva et al. 2012). At the other extreme, S. chilensis, S. mexicana, and S. pallida are not pathogenic, and inoculated animals are able to resolve the infection a few days after the challenge (Arrillaga-Moncrieff et al. 2009; Rodrigues et al. 2016a). Alternative methods such as the use of invertebrate models are available for assessing the virulence of Sporothrix, especially the larvae of Galleria mellonella, with results similar to those observed in traditional animal models (Freitas et al. 2015; Clavijo-Giraldo et al. 2016).
10.7