Non-traditional T cells are lymphocytes that can quickly detect the presence of microbes on mucosal and non-mucosal surfaces and protect tissue integrity during infections. In the respiratory mucosa, this protective function during bacterial and viral infections is performed by invariant T cells (MAIT).
Scientists from the UK found that during pulmonary infection with the bacterium Klebsiella pneumoniae, type I interferons (IFN-I) are responsible for activating MAIT cells and controlling their protective functions. Before this discovery, it was believed that:
- The T-cell antigen recognition receptor (TCR) activates MAIT cells during bacterial infections, is located on the surface of MAIT cells, and uses an antigen presentation mechanism. The TCR recognizes the antigens that the MR1 molecule captures and exposes to the cell surface. By these antigens, T-lymphocytes determine whether the cell in front of them is healthy or infected.
- MR1-independent activation occurs during viral infections. IFN-I promotes the activation of MAIT cells during a viral infection or when administered with an adenovirus vector vaccine. In addition, IFN-I may act synergistically with TCR signals to increase the effector functions of MAIT cells.
Type I interferons, which include IFN-alpha and IFN-beta, have a powerful immunomodulatory effect in viral infections. However, interferons can have protective and harmful effects during bacterial infections, depending on the bacterium.
Klebsiella pneumoniae is a bacterium that causes severe pneumonia, sepsis, and urinary tract infections. MAIT cells contribute to lung protection during K. pneumoniae infection. Control the activation and antimicrobial function of MAIT cells during bacterial pneumonia with interferon.
Study Results
- Activation of MAIT cells during pneumoniae infection is independent of the MR1 protein. Scientists conducted a study on mice infected with K. pneumoniae. K. pneumoniae induced MAIT cell activation. When the scientists blocked the MR1 protein before infecting the mice, it did not affect the activation and function of MAIT cells. Similar results were obtained for human cells.
- In MAIT cells, K. pneumoniae activates genes associated with the type I IFN signaling pathway and the antiviral response. When scientists compared which genes are activated in MAIT cells in response to K. pneumoniae, IFN-I, and influenza, it turned out that out of 401 activated genes:
- 40% were standard in K. pneumoniae, and IFN-I stimulated cells.
- 124 genes were shared by K. pneumoniae, IFN-I, and influenza stimulations.
- Most activated genes were associated with interferon, but 210 genes were activated exclusively by K. pneumoniae.
- IFN-I is necessary and sufficient for MAIT cell activation. When the scientists blocked interferon signaling in mouse or human lung cells, MAIT cell activation in response to K. pneumoniae was reduced. This process was independent of MR1. In addition, type I IFN controlled MAIT cell activation in live mice. Blocking the interferon signaling pathway before infecting mice with K. pneumoniae also decreased MAIT cell activation. Moreover, the impact on mouse and human MAIT cells with IFN-alpha was sufficient for their activation.
- Type I IFN controls the effector functions of MAIT cells. In response to K. pneumoniae, MAIT cells produced proteins responsible for the cytotoxic functions of cells: IFN-gamma, granzyme B, and, to a lesser extent, IL-17A. The secretion of these three proteins was independent of MR1, but type I IFN was required to produce granzyme B and IFN-gamma.
- The protective effect of MAIT cells is independent of MR1 but depends on intrinsic type I IFN signaling. Mice deficient in IFN-I signals are susceptible to K. pneumoniae infection. MAIT cells transferred from normal mice to these mice contributed to infection control. However, the protective effect was abolished when interferon signaling was blocked in the transferred cells.
- During K. pneumoniae infection, type I IFN stimulates MAIT cells to move from the lung parenchyma into the spaces near the bronchi, locally activating MAIT cells.
Conclusion
Type I interferons are required to protect the lungs from Klebsiella pneumoniae infection. K. pneumoniae activates genes associated with the type I interferon signaling pathway in MAIT cells. Type I IFNs are critical factors in the MAIT cellular response during K. pneumoniae infection.
IFN signaling is required for the activation and effector functions of MAIT cells. When infected with K. pneumoniae, MAIT cells respond to an inflammatory stimulus regardless of the detected antigen and trigger a response against the infection. The protective role of MAIT cells depends on internal type I interferon signaling.
Given the abundance of MAIT cells in the human body and their rapid response to inflammatory signals, type I IFNs may be a novel target for controlling MAIT cell function during infections.
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Reference
Type I interferons drive MAIT cell functions against bacterial pneumonia
