B7 Costimulation Is Critical for Host Control of Chronic Mycobacterium tuberculosis Infection

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.

Earle's balanced salts solution and rapamycin differentially regulate the Bacillus Calmette-Guérin-induced maturation of human dendritic cells

“…To determine the effect of EBSS or rapamycin on the maturation of BCG-infected DCs, we first analysed the role of EBSS or rapamycin in the maturation of uninfected DCs. CD86 (B7-2) is one of the most critical molecules for the initiation of the T-cell response, and B7-mediated co-stimulation is critical for the host to control chronic M. tuberculosis infection [14]. HLA-DR is a human MHC class II antigen that plays a major role in the cellular interactions that occur during antigen presentation [15].…”

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus

“…During M. tuberculosis infection, mice lacking either CD80 or CD86 alone have no phenotype; however, mice lacking both co-stimulatory ligands show delayed T cell priming and have fewer CD4+ and CD8+ T cells producing IFNγ in their lungs [69,70]. These mice are still capable of mounting a modest T cell response, suggesting that other co-stimulatory receptors or ligands may provide a signal 2 during tuberculosis.…”

Autophagy promotes BCG-induced maturation of human dendritic cells

“…1). CD86 (B7-2), which is expressed on the surface of DCs, is one the most critical molecules for the initiation of the T cell response [11], and B7-mediated co-stimulation is critical for the host to control chronic M. tuberculosis infections [12]. Importantly, DC maturation has been associated with the up-regulation of CD86.…”