CD11c⁺ CD103⁺ cells of Mycobacterium tuberculosis‐infected C57BL/6 but not of BALB/c mice induce a high frequency of interferon‐γ‐ or interleukin‐17‐producing CD4⁺ cells

Abstract

SummaryThe magnitude of the cellular adaptive immune response is critical for the control of Mycobacterium tuberculosis infection in the chronic phase. In addition, the genetic background is equally important for resistance or susceptibility to tuberculosis. In this study, we addressed whether lung populations of dendritic cells, obtained from genetically different hosts, would play a role in the magnitude and function of CD4 + populations generated after M. tuberculosis infection. directly associated with the host genetic background. Therefore, differences in the genetic background contribute to the identification of immunological biomarkers that can be used to design human assays to predict progression of M. tuberculosis infection.

Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis‐infected hosts

“…Our findings and those from other groups show that C57BL/6 mice exhibit a higher production of IFN‐ γ than BALB/c mice; this increased production is independent of the ability to better control lung bacterial replication . Recently, we described how CD11c + CD103 + cells, which were found at a high frequency in the lungs of infected C57BL/6 mice but not infected BALB/c mice (which presented a high frequency of CD11c + CD11b + cells), were associated with a high frequency of IFN‐ γ ‐ or IL‐17‐producing CD4 + cells …”

“…The lower and middle right lobes of the lungs and the spleen were washed with sterile PBS. Each tissue was placed in a Petri dish containing incomplete RPMI‐1640 medium (Sigma, St Louis, MO) and processed as previously reported . For determination of colony‐forming units (CFU), serial dilutions (100, 1000, 10 000 and 100 000) of the digested lungs and serial dilutions (10, 100, 1000 and 10 000) of the digested spleens were plated onto supplemented 7H11 agar media (Difco, Becton, Dickinson and Company, Le Pont de Chaix, France).…”

Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy

“…4c), suggesting CD40 axis dependence underlying the accelerated vaccine response in Z-DC transfer-recipient mice. Furthermore, Batf3 is a transcription factor that drives development of CD103 + DCs, which are important for priming Th1 and Th17 responses3435. Batf3 messenger RNA expression was increased in vaccinated Mtb -infected hosts receiving Z-DC transfer (Supplementary Fig.…”

“…CD103 + DCs are a tissue-resident DC subset, which have primarily been implicated in cross-presentation and induction of CD8 + T-cell responses5960. More recently, however, CD103 + DCs have been shown to induce CD4 + T cells343561. In the lung, CD103 + DCs represent a migratory DC subset, with the ability to migrate from the lungs to the LN and back again62, and induce both Th1 and Th17 cytokines by CD4 + T cells343563.…”

“…More recently, however, CD103 + DCs have been shown to induce CD4 + T cells343561. In the lung, CD103 + DCs represent a migratory DC subset, with the ability to migrate from the lungs to the LN and back again62, and induce both Th1 and Th17 cytokines by CD4 + T cells343563. Although antigen presentation by transferred DCs likely directly activates vaccine-induced CD4 + T-cell responses, rapid activation of CD4 + T-cell responses also modifies the lung micro-environment to improve subsequent antigen presentation by endogenous host APCs.…”