To explore the mechanisms that underlie the development of tertiary lymphoid tissue, the authors used models of lung infection that induce the development of bronchus-associated lymphoid tissue (BALT). In agreement with previous work, they found that a single intranasal challenge with the modified vaccinia virus Ankara (MVA) or the repeated intranasal administration of heat-killed Pseudomonas aeruginosa (a Gram-negative bacterial strain) induced BALT formation in mice. Notably, these challenges each induced distinct types of BALT; although both types of BALT contained CXC-chemokine ligand 12 (CXCL12)-expressing stromal cells and B cell follicles surrounded by T cell areas, only MVA-induced BALT contained CXCL13+ follicular dendritic cells (FDCs) or other CXCL13-expressing cells. Functionally, the absence of FDCs in P. aeruginosa-induced BALT was associated with impaired germinal centre formation, and fewer IgA+ plasma cells were detected in P. aeruginosa-induced BALT compared with MVA-induced BALT. However, both types of BALT contained equivalent numbers of IgG+ and IgM+ plasma cells.
In keeping with the absence of FDCs in P. aeruginosa-induced BALT, lymphotoxin-α1β2 (LTα1β2) — which drives the differentiation of these cells — was expressed by B cells from the lungs of MVA-infected mice but not by B cells from the lungs of P. aeruginosa-treated mice. Furthermore, the authors showed that the induction of B cell follicles in P. aeruginosa-induced BALT, but not in MVA-induced BALT, required interleukin-17 (IL-17). They found that IL-17 promoted the production of CXCL12 by pulmonary stromal cells and showed that this induction of CXCL12 is crucial for BALT formation in response to P. aeruginosa. By contrast, the development of B cell follicles in BALT was only inhibited in MVA-infected mice if signalling induced by CXCL12 and CXCL13 was blocked. Thus, the development of different types of BALT in response to these infections seems to be caused by the differential induction of CXCL12 and CXCL13 expression by the two pathogens.
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