Discontools supplement Mycoplasma hyopneumoniae infections in pigs: update and knowledge gaps

This manuscript reviews current knowledge on Mycoplasma hyopneumoniae, the primary agent of enzootic pneumonia in pigs, integrating advances in epidemiology, pathogenesis, immunity, diagnostics, and control. The pathogen is globally endemic, with transmission driven mainly by direct contact within a herd, and by purchase of animals and airborne transmission between herds. Infection dynamics are shaped by production systems, sow-piglet transmission, and co-infections, while strain diversity and subclinical infections complicate disease expression and control. Pathogenesis is understood as a complex, multifactorial phenomenon rather than being determined by single virulence factors. Adhesion, biofilm formation, extensive posttranslational processing, metabolic adaptation, and immune evasion collectively enable persistent colonization. A major conceptual advance is the discovery of migrasome-mediated dissemination, which may explain chronic infection and reduced antimicrobial efficacy.

Despite significant advances, important knowledge gaps remain in multiple areas of Mycoplasma hyopneumoniae research. Uncertainties persist in transmission and epidemiology, including the role of environmental spread, wild boar reservoirs, and the extent of subclinical infections. The impact of strain diversity on virulence, transmission, persistence, and vaccine performance is not yet fully understood, and predictive markers are lacking. Key aspects of host-pathogen interactions, such as immune evasion, occasional intracellular survival, macrophage polarization, and the in vivo relevance of migrasome-mediated dissemination, require further clarification. Protective immunity remains poorly defined, with unresolved questions on correlates of protection and the roles of mucosal and systemic responses. Diagnostic challenges include distinguishing active from residual infection and improving specificity and Differentiating Infected from Vaccinated Animals (DIVA) compatibility. Evidence on antimicrobial effects on transmission and resistance monitoring is limited. In addition, variability in vaccine efficacy and the influence of maternal immunity remain unclear. Finally, scalable elimination strategies, particularly for very large production systems and reduced antimicrobial use, are still needed.