Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity

Abstract

Bronchus-associated lymphoid tissue (BALT) is occasionally found in the lungs of mice and humans; however, its role in respiratory immunity is unknown. Here we show that mice lacking spleen, lymph nodes and Peyer's patches generate unexpectedly robust primary B- and T-cell responses to influenza, which seem to be initiated at sites of induced BALT (iBALT). Areas of iBALT have distinct B-cell follicles and T-cell areas, and support T and B-cell proliferation. The homeostatic chemokines CXCL13 and CCL21 are expressed independently of TNFalpha and lymphotoxin at sites of iBALT formation. In addition, mice with iBALT, but lacking peripheral lymphoid organs, clear influenza infection and survive higher doses of virus than do normal mice, indicating that immune responses generated in iBALT are not only protective, but potentially less pathologic, than systemic immune responses. Thus, iBALT functions as an inducible secondary lymphoid tissue for respiratory immune responses.

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

“…and Mycobacterium tuberculosis bacteria, as well as influenza and hepatitis C viruses, have been linked with ELF development in mice and humans 77, 78, 79, 80, 81, 82, 83, 84. Interestingly, ELF formation in response to infection features at mucosal sites including lung, gastric and salivary gland tissues 78, 82, 85. ELFs that develop in response to microbiota are also important for maintaining intestinal homeostasis 86.…”

“…There is considerable evidence linking ELFs with anti‐microbial and viral immunity. For example mice lacking spleen, lymph nodes and Peyer's patches mount robust B‐cell and T‐cell responses to influenza virus at sites of iBALT formation 82. Notably, in the absence of peripheral lymphoid organs, these mice tolerate higher virus doses than wild‐type mice, suggesting that the anti‐viral response generated at iBALT is not only protective but may also be less pathogenic than those generated in the periphery.…”

“…Notably, in the absence of peripheral lymphoid organs, these mice tolerate higher virus doses than wild‐type mice, suggesting that the anti‐viral response generated at iBALT is not only protective but may also be less pathogenic than those generated in the periphery. Mice were able to show effective primary and memory responses to viral challenge via ELFs, associated with the emergence of influenza‐specific CD8 T cells and anti‐influenza nucleoprotein‐specific antibodies 81, 82. Development of iBALT in response to infection was again linked to CXCL13 and CCL21 expression locally,82 but was also dependent on CD11c hi DCs 80.…”

The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact

“…It has, however, been reported that Tertiary Lymphoid Structures (TLS) are abundant in highly inflamed tissues resulting from chronic infections, auto-immune diseases or organ transplantation [38]. It has been demonstrated that efficient primary and secondary immune reactions can be generated in mice lacking lymph nodes [39,40]. In cancers, mature DC presenting tumor-associated antigens may migrate from the tumor to the draining lymph nodes and educate T and B lymphocytes [37].…”

The Role of Intrapulmonary De Novo Lymphoid Tissue in Obliterative Bronchiolitis after Lung Transplantation

“…Chronic rejection after lung transplantation is manifested by obliterative bronchiolitis (OB), a chronic inflammatory and fibroproliferative condition in small airways, and its clinical correlate, bronchiolitis obliterans syndrome (BOS) (10). In the lung, TLO is considered to be represented by an inducible form of bronchus-associated lymphoid tissue (BALT), namely iBALT (1,11). Formation of iBALT has been reported in various chronic inflammatory lung diseases such as emphysema (12), pulmonary fibrosis (13), and chronic hypersensitive pneumonitis (14).…”