Pathophysiological and immunological characterization of a murine excisional wound infection model for cutaneous...

Mycobacterium abscessus is an emerging rapidly growing nontuberculous mycobacterium that causes chronic skin and soft tissue infections, but its pathogenic potential remains difficult to assess in vivo because existing animal models do not fully recapitulate localized cutaneous infection.

We established a murine excisional wound infection model designed to mimic cutaneous barrier disruption and compared it with conventional subcutaneous inoculation. BALB/c mice were infected with a rough-morphotype clinical isolate or rough-morphotype ATCC 19977, and lesion development, bacterial recovery, histopathology, local cytokine mRNA expression, and serum cytokine/chemokine profiles were assessed at terminal time points.

Compared with subcutaneous injection, the wound model generated persistent lesions with histopathological features consistent with pyogranulomatous inflammation, including foamy macrophages, multinucleated giant cells, fibroblast proliferation, and localized interferon-gamma (IFNgamma) expression. In the strains tested, the model revealed strain-dependent differences in infection establishment: the clinical isolate produced frequent chronic nodular lesions, whereas roughmorphotype ATCC 19977 showed lower lesion incidence under the same experimental conditions. Local tissue and serum cytokine profiling demonstrated a T helper 1 (Th1)-skewed immune response detectable at both terminal time points, associated with bacterial recovery from infected tissues and detectable splenic bacterial recovery.

These findings suggest that the excisional wound model provides a clinically relevant platform for studying localized cutaneous M. abscessus infection. Further validation using additional clinical isolates and mechanistic studies will be required to define its broader applicability.