Immune Response toNocardia brasiliensisAntigens in an Experimental Model of Actinomycetoma in BALB/c Mice

Abstract

Nine- to twelve-week-old BALB/c mice were injected in footpads with 107 CFU of a Nocardia brasiliensis cell suspension. Typical actinomycetoma lesions, characterized by severe local inflammation with abscess and fistula formation, were fully established by day 28 after infection. These changes presented for 90 days, and then tissue repair with scar formation slowly appeared, with complete healing after 150 days of infection. Some animals developed bone destruction in the affected area. Histopathology showed an intense inflammatory response, with polymorphonuclear cells and hyaloid material around the colonies of the bacteria, some of which were discharged from draining abscesses. Sera from experimental animals were analyzed by Western blotting, and immunodominant antigens P61 and P24 were found as major targets for antibody response. Anti-P24 immunoglobulin M (IgM) isotype antibodies were present as early as 7 days, IgG peaking 45 days after infection. Lymphocyte proliferation with spleen and popliteal lymph node cells demonstrated thymidine incorporation at 7 days after infection, the stimulation index decreasing by day 60. Levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, tumor necrosis factor alpha, and gamma interferon (IFN-γ) were determined by enzyme-linked immunosorbent assay in the sera of infected animals. The circulating levels of IFN-γ increased more than 10 times the basal levels; levels of IL-4, IL-6 and IL-10 also increased during the first 4 days of infection.

A Polymorphism in the Chitotriosidase Gene Associated with Risk of Mycetoma Due to Madurella mycetomatis Mycetoma–A Retrospective Study

“…Based on immunohistochemistry studies in various mycetoma causative agents, it appeared that the cytokine pattern surrounding the mycetoma grain is a Th2 response. IL-10 and IL-4, both Th2-associated cytokines, were highly expressed around the fungal grain [ 7 , 26 , 27 ]. A different study showed that after stimulation of peripheral blood mononuclear cells (PBMCs) with mycetoma antigens, a Th2 response developed in mycetoma patients and a Th1 response developed in healthy endemic controls [ 25 ].…”

Retnla down-regulation and IL-13-rich environment correlate with inflammation severity in experimental actinomycetoma byNocardia brasiliensis

“…Mice were infected with 10 6 colony-forming units (CFU) of Nb, strain ATCC 700358, in the rear left footpad as previously described (Salinas-Carmona et al, 1999). The lesion size was monitored by measuring three diameters of the lesion with a Vernier and applying the formula for the volume of an ellipse.…”

“…Foamy macrophages are found just below the fibrotic layer that delimits a microabscess (Salinas-Carmona, 2000). To study hostpathogen interactions, we have established an experimental actinomycetoma in BALB/c mice, which is similar to the human lesion (Salinas-Carmona et al, 1999). Typically, the lesion size of the acute inflammation reaches its maximum about 1 week after inoculation.…”

“…Typically, the lesion size of the acute inflammation reaches its maximum about 1 week after inoculation. The chronic infection (actinomycetoma) develops after 4 weeks with a severe inflammation and tissue deformation (Salinas-Carmona et al, 1999).…”

“…The humoral immune response is also activated, in which, apart from IgG antibodies, relatively high sustained levels of IgM antibodies seem important for partial protection in a complement-independent way (Salinas-Carmona & Perez-Rivera, 2004;Gonzalez-Suarez et al, 2009). Cord factor, catalase, and superoxide dismutase have been identified as Nb's virulence factors (Salinas-Carmona et al, 1999Revol et al, 2006;Trevino-Villarreal et al, 2012). Theorizing that some bacteria escape from the immune response by hiding in non-hostile cells, we focused on the activation type of macrophages.…”