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Interactions Between M. hyopneumoniae and Other Pathogens

Interactions Between M. hyopneumoniae and Other Pathogens. Eileen L. Thacker DVM, PhD, DACVM Iowa State University. Porcine Respiratory Disease Complex (PRDC). Economically significant to the swine industry in the U.S. Pathogens Associated with PRDC. PRRSV Mycoplasma hyopneumoniae

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Interactions Between M. hyopneumoniae and Other Pathogens

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  1. Interactions Between M. hyopneumoniae and Other Pathogens Eileen L. Thacker DVM, PhD, DACVM Iowa State University

  2. Porcine Respiratory Disease Complex (PRDC) • Economically significant to the swine industry in the U.S.

  3. Pathogens Associated with PRDC • PRRSV • Mycoplasma hyopneumoniae • Swine influenza virus (SIV) • Actinobacillus pleuropneumoniae • Streptococcus suis • Pasteurella multocida • Aujeszky’s disease (Pseudorabies virus )

  4. Enzootic pneumonia • Mycoplasma hyopneumoniae • Mycoplasmal pneumonia • M. hyopneumoniae plus • Pasteurella multocida • Bordetella bronchiseptica • Haemophilus parasuis • Actinobacillus pleuropneumoniae • Etc.

  5. M. hyopneumoniae & P. multocida(Enzootic Pneumonia)

  6. PRDC • Enzootic pneumonia + • PRRSV • SIV • PCV 2?

  7. Which Diseases are Considered the Biggest Problem in PRDC? • Varies from farm-to-farm • Porcine respiratory disease complex common problem in finishing pigs • NOT in the scope of this talk to discuss all pathogens • results of current research

  8. Mycoplasma hyopneumoniae • Cause of “enzootic pneumonia” • Other secondary pathogens • APP • Pasteurella multocida • PRRSV • Clinical signs-M. hyopneumoniae alone • mild, dry, nonproductive cough

  9. Pathogenesis • Very slow to colonize and multiply • 2 weeks+ to induce observable lesions • 4-6 weeks before serum antibodies produced • 4-8 weeks to resolution • Organisms never eliminated from pig?

  10. Adheres only to cilia of airways • Does not invade lung tissues

  11. Disease • Decrease the function of the mucociliary apparatus • decrease clearance of other pathogens and debris • Modulation of the immune system • immunosuppression-macrophages - APP • immunostimulation-lymphocytes • cytokine production

  12. Pathology • Chronic pneumonia • 2-3 weeks for pneumonic lesions to appear • mild • focal, well-demarcated area of cranioventral consolidation

  13. Histopathology • Bronchopneumonia • Perivascular and peribronchiolar cuffing • Influx of lymphocytes and macrophages • primarily B cells • non-specific

  14. Evasion of the Immune System • Mucosal pathogen • location • Structure and make up of surface • slime layers • capsule • no cell wall

  15. Proinflammatory Cytokines • TNF- • IL-1 • IL-6 • Important in further inducing inflammation in the lungs

  16. Dual infection of Pigs with PRRSV and Mycoplasma hyopneumoniae E.L. Thacker, P.G. Halbur, B.J. Thacker and R. F. Ross Iowa State University

  17. Porcine Reproductive and Respiratory Syndrome Virus

  18. PRRSV • An Arterivirus • Enveloped RNA virus • all infect macrophages • all cause prolonged infections • High mutation rate due to method of replication = constant minor changes • Accounts for differences between “isolates” • No such thing as “strains”

  19. Clinical Signs • Severe to no clinical disease in the field • In our experimental model • maximum pneumonia is 10 days • fever, respiratory distress, lethargy, anorexia • no cough • pneumonia resolved by 21-28 days

  20. Pathology • Diffuse, tan-mottled consolidation of the lungs

  21. Evades the Immune System • Persists • > 100 days • Very slow to ineffective systemic immune response • viremia in presence of antibodies • can be reinfected by different strains • alteration of immune response by directing cytokines

  22. Experimental Design • Three different inoculation protocols • PRRSV first (-10 days) • M. hyopneumoniae first (-21 days) • concurrent (0 days) • Three necropsy dates • 3 DPI • 10 DPI – maximum PRRSV pneumonia • 28 DPI – maximum mycoplasma pneumonia

  23. Conclusions • Pigs infected with both M. hyopneumoniae and PRRSV: • S • significantly increased clinical respiratory disease • macroscopic lesions consistent with PRRSV-induced pneumonia lasted significantly longer • increased M. hyopneumoniae-induced pneumonia at 10 days post infection with both

  24. PRRSV - 28 DPI PRRSV- 10 DPI M. hyopneumoniae - 28 DPI Dual Infection - 28 DPI

  25. Conclusions (cont.) • No long term increase in M. hyopneumoniae-induced pneumonia macroscopically • Pigs with minimal to no macroscopic mycoplasmal pneumonia lesions exhibited potentiation of PRRSV-induced pneumonia

  26. WHY? • Pathogenesis complement each other • M. hyopneumoniae attracts macrophages for PRRSV to infect • both induce inflammation • both direct the immune response from a Th1 towards a Th2 response • production of IFN-γ is correlated to virus clearance • delayed in pigs infected with both pathogens

  27. Why? • Immune system • both evade the immune system • both modulate the immune system • both chronic • PRRSV-persistance • M. hyopneumoniae chronic

  28. Interaction between M. hyopneumoniae and SIV E. Thacker, B. Thacker and B. Janke Iowa State University

  29. M. hyo infect epithelial cells (cilia) causes a chronic pneumonia SIV infects epithelial cells causes acute pneumonia – but will last 3+ weeks histologically What do we know

  30. Experimental Design • M. hyopneumoniae strain 232 intratracheally (-21 Trial Day) • ISU SIV inoculum (H1N1) nebulized intranasally (0 Trial Day) • Pigs necropsied at 3, 7, 14 and 21 days post SIV infection

  31. Confusing Appearance

  32. Results • Dual infected pigs had highest coughing scores • Pneumonia lasted longer-additive in nature

  33. Conclusions • Unlike with PRRSV, SIV and M. hyopneumoniae appear to be additive • Both infect epithelial cells – important for secondary pathogens • Different pathogenesis than with PRRSV

  34. Circovirus (PMWS)

  35. PCV 2 alone induces minimal disease • Combined with PRRSV, Porcine Parvovirus results in significant increase in pneumonia • Interaction and role of M. hyopneumoniae? • Role of vaccination? • Mechanism is unknown • Can bet immune system is involved

  36. Conclusions • M. hyopneumoniae and PRRSV are both important factors in PRDC • The pigs in our studies had no other pathogens • these contribute to and interact with each other • These studies are aimed at beginning to understand the interaction between the various pathogens

  37. Conclusions (cont.) • PCV 2 increasing in importance of disease interactions • Other pathogens such as P. multocida and B. bronchiseptica present add to the disease • Diagnostics become very important on individual farm settings to implement the appropriate controls

  38. Conclusions (cont.) • As our understanding of the pathogenesis increases, appropriate intervention strategies can be developed • vaccines – very important • new and current • antibiotics • strategic timing of above

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