Passive immunization does not provide protection against experimental infection with Mycoplasma haemofelis

Sugiarto, Sarah; Spiri, Andrea M.; Riond, Barbara; Novacco, Marilisa; Oestmann, Angelina; de Miranda, Luisa H. Monteiro; Meli, Marina L.; Boretti, Felicitas S.; Hofmann-Lehmann, Regina; Willi, Barbara

The natural route of hemoplasma transmission between cats is still unresolved, but aggressive interactions and blood-sucking arthropods have mainly been implicated [17] [18] [19] . For experimental transmission, the intraperitoneal, intravenous or subcutaneous inoculation of hemoplasma-containing blood has been successful [10, [19] [20] [21] . Recently, a low-dose infection model for Mhf that aimed to more accurately mirror the natural transmission of hemoplasmas was developed [22] . Different antibiotic regimens reduce hemoplasma blood loads and alleviate clinical signs but, so far, no treatment protocol has successfully and consistently cleared feline hemoplasma infections [21, [23] [24] [25] [26] . This limitation emphasizes the need to further investigate protective immune mechanisms against these agents. Recently, cats that were experimentally infected with Mhf or CMt and overcame bacteremia were shown to be protected from reinfection with the same hemoplasma species [27, 28] . A study by Novacco et al. [27] suggested a significant role for the humoral immune response in protecting against CMt reinfection: nine out of the ten cats that were protected from reinfection showed intermediate to high antibody levels against CMt before challenge. Furthermore, a transient decrease in antibody levels was observed in the protected cats immediately after attempted reinfection, which could be due to the binding of antibodies to the inoculated antigens. In the early phase after re-challenge, compared with the control group, the protected cats exhibited significantly higher IL-4/IL-12 ratios and CD4 + T lymphocyte counts and a pronounced eosinophilia. Therefore, the authors concluded that an early Th2 immune response, prior to the onset of bacteremia, is beneficial for protection against CMt reinfection [27] . This result was not found in the study by Hicks et al. [28] , where an early increase in the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was observed in cats protected from Mhf reinfection. Furthermore, the immune response seemed to be skewed towards a Th1 response after primary Mhf infection, whereas a switch from an initial Th1 to a delayed Th2 response was observed after primary CMt infection [27, 28] . These results suggest that cats respond to infection by different feline hemoplasma species with different immune mechanisms.