Increased apoptosis during the early phase of experimental paracoccidioidomycosis as a phenotypic marker of resistance

• Published in: Microbes and infection Vol. 8; no. 12; pp. 2811 - 2820
• Main Authors: Verícimo, Maurício A., França, Karla Marcelino, Arnholdt, Andrea C.V., Kipnis, Thereza L.
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01.10.2006; Amsterdam Elsevier; Paris
• Subjects: Animals; Apoptosis; Biological and medical sciences; Blastomycoses and paracoccidioidomycosis; Cells, Cultured; Disease Models, Animal; Fas; Fas Ligand Protein - biosynthesis; fas Receptor - biosynthesis; FasL; Fundamental and applied biological sciences. Psychology; Human mycoses; Immunity, Innate; Infectious diseases; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-1beta - biosynthesis; Interleukin-6 - biosynthesis; Macrophages, Peritoneal - physiology; Medical sciences; Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Knockout; Microbiology; Mycoses; Nitric Oxide - biosynthesis; P. brasiliensis; Paracoccidioides - immunology; Paracoccidioidomycosis - immunology; Paracoccidioidomycosis - physiopathology; Tropical mycoses; P. brasiliensis; FasL; Fas; PCM; L-NMMA; LPS; Apoptosis; Fas ligand; Blastomycosis; Mycosis; Cytokine; Infection; Resistance; Cell death; Fas Antigen; Paracoccidioidomycosis
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2006.08.012

Paracoccidiodomycosis (PCM) is a systemic mycosis that presents a wide spectrum of clinical manifestations caused by Paracoccidiodes brasiliensis. The experimental murine model has been used to approach the disease with susceptible and resistant mouse strains that reproduce most of the main human immunological features. We investigated whether the pattern of apoptosis of peritoneal cells from two polar strains of mice after infection with P. brasiliensis could be associated with the susceptibility or resistance to this pathogen. Apoptosis of A/J mouse cells (resistant), cultured in the presence or absence of LPS as stimuli, was observed as early as on the first day of infection. Cells from the infected susceptible strain BALB/c did not exhibit apoptosis in absence of LPS and persistently at a lesser degree than that observed in resistant mice. The apoptosis induced by the infection in resistant mice was not due to nitric oxide, since its blockage either in vitro or in vivo did not revert it. Analysis of additional strains of polar susceptibilities to PCM assured the dissociation of NO production and apoptosis. Interestingly, IL-6 and IL-10 were secreted in high amounts, by BALB/c cells and might be involved in shielding cells from apoptosis induced by P. brasiliensis. Furthermore, IFNγ −/− mice did not show apoptosis of peritoneal cells while the Wt controls presented levels similar to those of A/J strain that secreted high amounts of IFNγ and IL-1β. The expression of Fas was increased in both strains and in Wt mice, whereas FasL was decreased in the susceptible strain and not significantly modulated in TNFRI and IFNγ KO mice. These results suggest that apoptosis might be a mechanism of control of engagement of cells that could otherwise contribute to the susceptible phenotype observed in some strains of mice.