Antibody-associated responses are linked to increased susceptibility to Rhodococcus equi infection in mice.

Rhodococcus equi is an intracellular pathogen that causes pyogranulomatous pneumonia in foals through replication within macrophages. Protective immunity is generally attributed to T helper 1 (Th1)-type cellular responses, although the mechanisms underlying effective immunity remain incompletely defined. In this study, we assessed the immunological responses to various R. equi-derived antigen preparations in a murine model. Immunization with live R. equi protected against bacterial proliferation following challenge, whereas immunization with formalin-killed bacteria increased the bacterial burden. Similarly, immunization with bacterial components or secreted products lacking defined antigen specificity resulted in enhanced susceptibility to infection and increased mortality. Antibody analysis revealed that IgG derived from immunized mice significantly enhanced intracellular R. equi proliferation in vitro. These findings suggest that antibody-mediated uptake may contribute to intracellular survival and replication of R. equi. These observations are consistent with an antibody-dependent enhancement (ADE)-like phenomenon in this experimental model. Conversely, live immunization induced a CD8+ T cell-skewed response following infection. Collectively, these results indicate that antibody-associated humoral immunity is associated with disease exacerbation, whereas Th1-type cellular immunity correlates with protective immunity against R. equi infection.IMPORTANCERhodococcus equi is a major cause of severe pneumonia in foals, and effective vaccines remain unavailable. Recent studies have suggested that antibody responses can have complex effects during bacterial infections; however, their roles in R. equi infection remain poorly understood. In this study, we demonstrated that immunization with nonviable R. equi antigens induces antibody responses associated with increased bacterial burden and disease severity. These antibodies increased intracellular bacterial loads of R. equi in vitro, suggesting that antibody-mediated uptake may facilitate intracellular survival and replication in this experimental model. Contrarily, protective immunity induced by live bacteria was associated with T helper 1 (Th1)-biased responses and early CD8+ T cell expansion. These findings highlight the importance of considering the balance between humoral and cellular immunity in vaccine development and underscore the need for strategies that elicit protective Th1-driven cellular immunity against R. equi infection.