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 M. hyopneumoniae plus
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

17. 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

18. Porcine Reproductive and Respiratory Syndrome Virus

19. 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”

20. 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 days

21. Pathology
Diffuse, tan-mottled consolidation of the lungs

22. 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

23. 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

26. 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

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

28. 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

29. 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

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

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

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

33. 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

36. Confusing Appearance

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

38. 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

39. Circovirus (PMWS)

40. 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

41. 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

42. 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

43. 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