Synergistic pathogenicity in sequential coinfection with Mycoplasma hyorhinis and porcine circovirus type 2

• The mixed infection of PCV2 and Mhr is prevalently existed around the world.
• The dual-infections of Mhr and PCV2 induced more severe respiratory diseases and organ lesions.
• Various degrees of synergistic pathogenicity were found in the sequential infection.
• The dual-infection models will be very useful for vaccination and antimicrobial intervention strategies of PCV2.

To investigate the synergistic pathogenicity of Mycoplasma hyorhinis (Mhr) with porcine circovirus type 2 (PCV2), thirty 35-day-old piglets were randomly distributed to six groups (n = 5 each): Mhr/PCV2 (group 1, inoculated with Mhr and PCV2 1 week later), PCV2/Mhr (group 2, inoculated with PCV2 and Mhr 1 week later), Mhr–PCV2 (group 3, inoculated with PCV2 and Mhr concurrently), singular PCV2 group (group 4), singular Mhr group (group 5), and a uninfected control group (group 6). Mild transient lethargy, fever, coughing, inappetence, and decreased daily weight gain were observed in all dual-infected groups and the singular Mhr-infected group. There were significantly higher levels of PCV2 and Mhr antibodies, larger amounts and wider range of tissue distribution of PCV2 antigens and nucleic acids in the dual-infected groups compared to the single-infected and control groups. PCV2 and Mhr dual-infection resulted in significantly more severe macroscopic and microscopic lung lesions and wider PCV2 DNA distribution compared with piglets infected with PCV2 alone. Cytokine detection showed a significant change in tumor necrosis factor-α, interleukin-2, and interleukin-6 levels in the infected groups, especially in the Mhr–PCV2 group, compared with the control group. Hence, Mhr potentiated the severity of PCV2-associated lung lesions, increased the amount and distribution of PCV2 DNA in tissues, and increased the incidence of porcine respiratory disease.