Persistence of Brucella abortus in the Bone Marrow of Infected Mice

Cristina Gutiérrez-Jiménez1, Lisiena Hysenaj2, Alejandro Alfaro-Alarcón3

  • 1Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

Insights

Brucellosis bacteria persist in bone marrow (BM), causing chronic infections and potential relapses. Infected myeloid progenitors, neutrophils (PMNs), and monocytes act as reservoirs and vehicles for Brucella persistence.

Area of Science:

  • Microbiology
  • Immunology
  • Infectious Diseases

Background:

  • Brucellosis is a zoonotic bacterial infection known for persistent infections and relapses, even after antibiotic treatment.
  • The ability of Brucella to establish chronic infections is linked to its capacity to invade and replicate within the mononuclear phagocyte system, including bone marrow (BM).
  • Brucella persistence in the BM is associated with hematological complications like neutropenia, thrombocytopenia, anemia, and pancytopenia in human patients.

Purpose of the Study:

  • To investigate the role of the bone marrow (BM) as a niche for Brucella persistence.
  • To identify the specific cell types within the BM that harbor Brucella during chronic infection.
  • To explore the mechanisms by which Brucella establishes long-lasting infections in the BM.

Main Methods:

  • Utilized a mouse model to study Brucella abortus infection.
  • Monitored Brucella numbers in the BM up to 168 days postinfection.
  • Performed histopathological analysis of the BM.
  • Quantified specific cell populations including myeloid GMP progenitors, PMNs, and CD4+ lymphocytes.
  • Identified Brucella-harboring cells within the BM.

Main Results:

  • Brucella abortus numbers remained constant in the BM for up to 168 days postinfection.
  • Persistence was associated with histopathological changes in the BM.
  • An increased number of BM myeloid GMP progenitors, PMNs, and CD4+ lymphocytes were observed during the acute phase of infection.
  • Monocytes, PMNs, and GMP cells were identified as the primary cells harboring Brucella in the BM.

Conclusions:

  • The bone marrow (BM) serves as an essential niche for Brucella to establish long-lasting infections.
  • Infected PMNs (polymorphonuclear neutrophils) may act as 'Trojan horses' for Brucella dispersion.
  • Monocytes are identified as strong candidates for Brucella reservoirs within the BM, contributing to chronic infection persistence.

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