AUTHOR=Stranahan Lauren W. , Garcia-Gonzalez Daniel G. , Hensel Martha E. , Arenas-Gamboa Angela M. 

TITLE=Primary and memory immune responses against rough Brucella canis are less robust compared to smooth B. abortus and B. melitensis following intratracheal infection in mice

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.959328

DOI=10.3389/fimmu.2022.959328

ISSN=1664-3224

ABSTRACT=<p><italic>Brucella canis</italic> is the cause of canine brucellosis, a globally distributed, zoonotic pathogen which primarily causes disease in dogs. <italic>B. canis</italic> is unique amongst the zoonotic <italic>Brucella</italic> spp. with its rough lipopolysaccharide, a trait typically associated with attenuation in gram-negative bacteria. Unfortunately, no vaccine is available against <italic>B. canis</italic>, and vaccine development is hampered by a limited understanding of the immune response required to combat it and the course of infection following a physiologically relevant, mucosal route of inoculation. To address these concerns and analyze the impact of the rough phenotype on the immune response, we infected mice intratracheally with rough <italic>B. canis</italic> or smooth <italic>B. melitensis</italic> or <italic>B. abortus</italic>. Bacterial colonization and histologic lesions were assessed in systemic target organs as well as locally in the lungs and draining mediastinal lymph node. Mice were also reinfected with <italic>Brucella</italic> following antibiotic treatment and cytokine production by T lymphocytes in the lung and spleen was assessed by flow cytometry to investigate the memory immune response. Despite its rough phenotype, <italic>B. canis</italic> established a persistent infection at the same level of colonization as the smooth strains. However, <italic>B. canis</italic> induced significantly less granulomatous inflammation in the spleen as well as a lack of bronchial-associated lymphoid tissue (BALT) hyperplasia in the lungs. These differences coincided with increased IL-10 and decreased IFN-γ in the spleen of <italic>B. canis</italic>-infected mice. Previous exposure to all <italic>Brucella</italic> strains provided protection against colonization following secondary challenge, although induction of IFN-γ by T lymphocytes was seen only in the lungs during <italic>B. canis</italic> infection while the smooth strains induced this cytokine in the spleen as well. Neither <italic>Brucella</italic> strain induced significant polyfunctional T lymphocytes, a potential immunomodulatory mechanism that appears to be independent of lipopolysaccharide phenotype.</p>