B7 costimulation is critical for host control of chronic Mycobacterium tuberculosis infection

Kamlesh Bhatt, Aleksandra Uzelac, Sanjeev Mathur, Amanda McBride, Julius Potian, Padmini Salgame

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Although much is understood regarding the role of B7/CD28 family of costimulatory molecules in regulating host resistance in the context of several pathogens, analogous information with Mycobacterium tuberculosis is lacking. To address the requirements of B7-mediated costimulation in host resistance against tuberculosis, mice deficient in both B7.1 and B7.2 (B7DKO) were aerosol infected with M. tuberculosis Erdman and disease progression was monitored. We report herein that B7DKO mice are initially able to contain the bacterial load in the lung, but exhibit enhanced susceptibility during chronic infection. Despite the early control of bacterial replication, B7DKO mice essentially start off with compromised Th1 immunity and slower granulomatous response in the lung, characterized by markedly reduced lymphocytic infiltration. As the infection progresses from acute phase to the chronic phase, the nascent granulomas in the B7DKO lungs never fully achieve the architecture of granulomas developing in wild-type mice. Instead, lesions spread progressively to involve much of the lung in the B7DKO mice, ultimately leading to necrosis. Thus, early control of M. tuberculosis growth in the lung can occur in the absence of B7 costimulation and is less dependent on Th1 immunity and formation of a granulomatous structure. However, B7 costimulation is critical for long-term containment of infection within lung granulomas. These findings suggest that the use of costimulation-based immunomodulators may have significant repercussions on the induction of host protective immunity against tuberculosis.

Original languageEnglish (US)
Pages (from-to)3793-3800
Number of pages8
JournalJournal of Immunology
Volume182
Issue number6
DOIs
StatePublished - Mar 15 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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