It is possible that during long lasting chronic infections such as tuberculosis (TB) and leprosy individuals who generate a stronger immune response will produce a chronic shift in the systemic levels of inflammatory proteins. Consequently, the systemic immunological shift could affect inflammatory responses against other persistent pathogens such as Porphyromonas gingivalis associated with periodontal disease (PD). Objective To determine if in vitro exposure to Mycobacterium tuberculosis or M. leprae lysates impacts subsequent immune responses to P. gingivalis; and to propose a new dialogue between experimental immunology and paleopathology. Material and methods We sequentially (2 days protocol) exposed peripheral blood mononuclear cells (PBMCs) from healthy donors to bacterial lysates either from M. tuberculosis, or M. leprae, or P. gingivalis. After collecting all supernatants, we measured the expression of immune proteins TNFα and IFNγ using an enzyme‐linked immunosorbent assay. Results Early exposure (day 1) of PBMCs to M. leprae or M. tuberculosis lysates induces an inflammatory shift detected by the increase of TNFα and IFNγ when the same cells are subsequently (day 2) exposed to oral pathogen P. gingivalis. Discussion By extrapolating these results, we suggest that chronic infections, such as TB and leprosy, could generate a systemic immunological shift that can affect other inflammatory processes such the one present in PD. We propose that the presence and severity of PD should be explored as a proxy for inflammatory status or competence when reconstructing the health profile in past populations.