Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the Guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviaecontaining eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs). Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only Guinea pigs infected with the higher doses showed significant changes in C. caviaespecific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within Guinea pigs' submandibular lymph node (SMLN) lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected Guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.
Filipovic, A., Ghasemian, E., Inic-Kanada, A., Lukic, I., Stein, E., Marinkovic, E., … Barisani-Asenbauer, T. (2017). The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection. PLoS ONE, 12(7). https://doi.org/10.1371/journal.pone.0180551