Accumulating studies have demonstrated that Bartonella henselae is associated with a spectrum of human diseases including cat-scratch disease (CSD), bacillary angiomatosis, peliosis hepatis, endocarditis, relapsing fever and bacteremia in both immunocompetent and immunocompromised persons (6,18,25,(27)(28)(29). It has been found that bacteremic cats play an important role as a reservoir of B. henselae (5,13,22). Despite high levels of bacteria in cats for many months, most bacteremic cats are asymptomatic, and the pathogenesis and mechanisms of the establishment of persistent infection by B. henselae in cats are not fully understood (9, 17).B. henselae invades feline erythrocytes and endothelial cells, suggesting that the agent belongs to an intracellular pathogen (15). Cell-mediated immunity (CMI) is believed to play significant roles in excluding intracellular pathogens. To evaluate the functions of CMI and humoral immunity (HI), examining the cytokine expression levels in T-lymphocytes is considered important. Because it has not been possible to assess the feline cytokine expression, there has been no information about the effectiveness of CMI against B. henselae infection in cats.In the present study, we used a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate the induction of feline gamma-interferon (IFN-γ) and feline interleukin 4 (IL-4), which are representatives of activations of T helper 1 (Th1) and T helper 2 (Th2), respectively. Furthermore, the mRNA expressions of tumor necrosis factor alpha (TNF-α), which is a key cytokine inducing the Th1 responses, were also examined by quantitative RT-PCR (32). The relationship between the levels of bacteremia and the Th1/Th2 cytokines were examined by using three naturally B. henselae infected cats showing relapsing bacteremia. were observed in PBMC from these infected cats after the bacteremia had peaked, showing that the T helper 2 (Th2) responses were specifically induced in the cats. Furthermore, the specific antibody titer increased, resulting in a decrease in the number of B. henselae to undetectable levels in these cats. However, the number of bacteria increased again in two of these cats at 90 and 45 days after the previous bacteremia, respectively. These results suggest that B. henselae predominantly induced IL-4 production from PBMC and resulted in stimulation of the humoral immune responses, including the secretion of specific antibodies in the cats. Furthermore, the specific antibody may play a role in eliminating the bacteria from cats partially but not completely, because relapsing bacteremia was found in these two cats.
Predominant T Helper 2 Immune Responses against