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Innate Immune Cell Swarms: Integrating and Adapting Single Cell and Population Dynamics in Inflamed and Infected Tissues

Innate Immune Cell Swarms: Integrating and Adapting Single Cell and Population Dynamics in Inflamed and Infected Tissues

Objective

Neutrophils are essential effector cells of the innate immune response. Intravital microscopy studies have recently changed our perspective on neutrophil tissue dynamics. They revealed swarm-like migration patterns in several models of inflammation and infection: Neutrophil populations show strikingly coordinated behavior with phases of highly directed chemotaxis and clustering at local sites of tissue damage. My previous work established that neutrophils self-amplify this swarming response by auto-signaling, which provided the first molecular basis for the collective nature of neutrophil swarms (Lämmermann et al., Nature 2013). However, we are still at the beginning of unraveling the molecular pathways behind this newly discovered phenomenon.

Most importantly, we completely lack insight into the signals and mechanisms that stop neutrophil swarms in the resolution phase of an immune response. Since excess neutrophil accumulations cause deleterious tissue destruction in many inflammatory diseases, novel insights into the mechanisms, which prevent extensive swarm aggregation, might be of considerable therapeutic value. In accord with this, our proposal follows three aims: (i) dissecting the cellular and molecular mechanisms that control the resolution phase of neutrophil swarming, (ii) establishing a conceptual framework of how swarming immune cells adapt their dynamics to changing inflammatory milieus, and (iii) developing an integrated view on how neutrophil swarms are controlled by secondary waves of myeloid cell swarms. To achieve our goals, we will combine targeted mouse genetics with live cell imaging of immune cell dynamics in living tissues and the use of innovative mimics of physiological environments.

Our future findings on innate immune cell swarms promise to (i) advance our knowledge on leukocyte navigation in complex inflammatory tissues and (ii) provide new avenues for the therapeutic modulation of tissue regeneration after inflammation and infection.
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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Address

Hofgartenstrasse 8
80539 Munich

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 500 000

Beneficiaries (1)

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MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 1 500 000

Project information

Grant agreement ID: 715890

Status

Ongoing project

  • Start date

    1 February 2017

  • End date

    31 January 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 500 000

  • EU contribution

    € 1 500 000

Hosted by:

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany