Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming

Evelyn Strickland; Deng Pan; Christian Godfrey; Julia S Kim; Alex Hopke; Maureen Degrange; Bryant Villavicencio; Michael K Mansour; Christa S Zerbe; Daniel Irimia; Ariel Amir; Orion D Weiner

doi:10.1101/2023.06.27.546744

Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming

bioRxiv [Preprint]. 2023 Jun 28:2023.06.27.546744. doi: 10.1101/2023.06.27.546744.

Authors

Evelyn Strickland^{1

2}, Deng Pan³, Christian Godfrey^{4

5}, Julia S Kim^{1

6}, Alex Hopke^{4

5}, Maureen Degrange⁷, Bryant Villavicencio⁸, Michael K Mansour^{5

9}, Christa S Zerbe¹⁰, Daniel Irimia^{4

5}, Ariel Amir^{3

11}, Orion D Weiner^{1

2}

Affiliations

¹ Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
² Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
³ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
⁴ BioMEMS Resource Center and Center for Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
⁵ Harvard Medical School, Boston, MA, USA.
⁶ Tetrad Graduate Program, UCSF, San Francisco, CA, USA.
⁷ Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
⁸ Kelly Government Services, Bethesda, MD, USA.
⁹ Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
¹¹ Department of Complex Systems, Faculty of Physics, The Weizmann Institute of Science, Rehovot 7610001, Israel.

Abstract

Neutrophils exhibit self-amplified swarming to sites of injury and infection. How swarming is controlled to ensure the proper level of neutrophil recruitment is unknown. Using an ex vivo model of infection, we find that human neutrophils use active relay to generate multiple pulsatile waves of swarming signals. Unlike classic active relay systems such as action potentials, neutrophil swarming relay waves are self-extinguishing, limiting the spatial range of cell recruitment. We identify an NADPH-oxidase-based negative feedback loop that is needed for this self-extinguishing behavior. Through this circuit, neutrophils adjust the number and size of swarming waves for homeostatic levels of cell recruitment over a wide range of initial cell densities. We link a broken homeostat to neutrophil over-recruitment in the context of human chronic granulomatous disease.

Keywords: CGD; biological self-organization; chemotaxis; collective migration; neutrophil swarming; self-extinguishing relay.

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Preprint

Abstract

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