Mycopathologia 144: 9–14, 1999. © 1999 Kluwer Academic Publishers. Printed in the Netherlands. 9 Host organism defense by a peptide-polysaccharide extracted from the fungus Sporothrix schenckii Iracilda Zeppone Carlos 1 , Diana Bridon da Graça Sgarbi 2 & Marisa Campos Polesi Placeres 1 1 Departamento de An´ alises Cl´ ınicas, Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Paulista J´ ulio Mesquita Filho, Araraquara, SP, Brasil; 2 Departamento de Microbiologia e Parasitologia, Instituto Biom´ edico, Universidade Federal Fluminense, Niter´ oi, RJ, Brasil Received 9 February 1998; accepted in revised form 11 January 1999 Abstract A peptide-polysaccharide, a peptide-rhamnomannan, was isolated from the pathogenic yeast form of the fungus Sporothrix schenckii. This substance, which may play a role in fungal virulence, was tested in an animal model of systemic disease, and depression of the immune response was observed in the animals between the 4th and 6th week of infection. Concomitantly, this compound showed mitogenic activity when challenged with normal lymphocytes and was also found to be involved in the inflammatory response. These results provide further information for the understanding of fungal implantation in tissues and of the pathogenicity of this systemic mycosis. Key words: immune and inflammatory responses, mitogenic activity peptide-polysaccharide, Sporothrix schenckii. Introduction Sporotrichosis is a worldwide spread mycosis mostly seen in tropical regions [1]. The disease often mani- fests as a chronic and granulomatous infection show- ing nodular lesions of cutaneous or subcutaneous tissues associated with localized lymphangitis and lymphadenopathy [2–5]. The systemic form of the dis- ease is likely to be more serious and hard to diagnose, resembling other infectious diseases. Indeed, more in- formation is necessary to explain its evolution inside the host. The immunological mechanisms involved in the prevention and control of sporotrichosis are not fully understood, but obviously include both the humoral [6–9] and the cellular [10–15] response. It is widely accepted that a suppressed immune response may be a precondition for clinical infection with yeast like S. schenckii and other mycotic agents. However, local or systemic infections may occur because of this mi- croorganism even in the absence of immune system alterations. Among the most intensively studied antigenic components of S. schenckii, the fraction peptide- rhamnomannan has been frequently used in serologic and skin tests [16, 17]. In a previous study [15], we developed a mur- ine model of disseminated sporotrichosis. Early stud- ies showed delayed hypersensitivity and depressed lymphocyte transformation between the 4th and 6th week of infection when the soluble antigen was used [18]. The production of interleukin-1 (IL-1) and tu- mor necrosis factor (TNF) by adherent peritoneal cells from S. schenckii in infected mice was also severely re- duced during the same period (4th and 6th weeks) and was increased after the 8th and 10th week of infection [19]. This depression frequently indicates a worsening of the disease, with greater involvement of the host. In the present report we examined the cellular immune and inflammatory responses in an animal model of disseminated sporotrichosis infection. We demonstrated the occurrence of a depressed immune response detected with an exoantigen, with involve- ment of the inflammatory response. Also, the peptide- rhamnomannan fraction was found to have mitogenic activity.