Complement factor P is a ligand for the natural killer cell-activating receptor NKp46

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Innate lymphoid cells (ILCs) are critical immune cells responding to microbes and stressed cells.
• ILCs utilize cell surface receptors to detect targets, but some ligands remain unidentified.
• NKp46 is a conserved receptor on natural killer (NK) cells and certain ILC subsets.

Purpose of the Study:

• To identify the ligand for the NKp46 receptor.
• To investigate the role of NKp46 and its ligand in immune responses, particularly against bacterial infections.

Main Methods:

• Biochemical assays to determine NKp46 binding partners.
• In vivo studies using mouse models of bacterial infection (Neisseria meningitidis).
• Genetic manipulation to assess the role of NKp46 and ILCs in infection survival.

Main Results:

• NKp46 directly binds to complement factor P (CFP), a regulator of the alternative complement pathway.
• Mice lacking CFP are susceptible to Neisseria meningitidis infection.
• NKp46 and group 1 ILCs are essential for survival against Neisseria meningitidis.
• CFP treatment efficacy in Neisseria meningitidis infection depends on NKp46 and group 1 ILCs.

Conclusions:

• Group 1 NKp46+ ILCs interact with the complement system via NKp46.
• This study reveals a novel cross-talk between ILCs and the complement pathway in innate immunity.
• The NKp46-CFP interaction is vital for combating invasive bacterial infections.