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

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Science Immunology  28 Apr 2017:
Vol. 2, Issue 10, eaam9628
DOI: 10.1126/sciimmunol.aam9628

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Inter-innate cooperation

The different branches of the immune system work together like a well-oiled machine, but how this coordination occurs is less well understood. Narni-Mancinelli et al. have found one such mechanism—cross-talk between the alternative complement pathway and natural killer (NK) cells and innate lymphoid cells (ILCs). They report that complement factor P (CFP), a positive regulator of the alternative complement pathway, binds NKp46, which is expressed on subsets of NK cells and ILC1 and ILC3. Patients lacking CFP are more susceptible to Neisseria meningitidis infection, and in mice, this CFP protection was dependent on NKp46 and group 1 ILCs. These data suggest that ILCs and the alternative complement pathway cooperate to fight off bacterial infection.

Abstract

Innate lymphoid cells (ILCs) are involved in immune responses to microbes and various stressed cells, such as tumor cells. They include group 1 [such as natural killer (NK) cells and ILC1], group 2, and group 3 ILCs. Besides their capacity to respond to cytokines, ILCs detect their targets through a series of cell surface–activating receptors recognizing microbial and nonmicrobial ligands. The nature of some of these ligands remains unclear, limiting our understanding of ILC biology. We focused on NKp46, which is highly conserved in mammals and expressed by all mature NK cells and subsets of ILC1 and ILC3. We show here that NKp46 binds to a soluble plasma glycoprotein, the complement factor P (CFP; properdin), the only known positive regulator of the alternative complement pathway. Consistent with the selective predisposition of patients lacking CFP to lethal Neisseria meningitidis (Nm) infections, NKp46 and group 1 ILCs bearing this receptor were found to be required for mice to survive Nm infection. Moreover, the beneficial effects of CFP treatment for Nm infection were dependent on NKp46 and group 1 NKp46+ ILCs. Thus, group 1 NKp46+ ILCs interact with the complement pathway, via NKp46, revealing a cross-talk between two partners of innate immunity in the response to an invasive bacterial infection.

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