Neutrophils instruct homeostatic and pathological states in naive tissues

Maria Casanova‑Acebes, José A. Nicolás‑Ávila, Jackson Liang Yao Li, Susana García‑Silva, Akhila Balachander, Andrea Rubio‑Ponce, Linnea A. Weiss, José M. Adrover, Kyle Burrows, Noelia A‑González, Ivan Ballesteros, Sapna Devi, Juan A. Quintana, Georgiana Crainiciuc, Magdalena Leiva, Matthias Gunzer, Christian Weber, Takashi Nagasawa, Oliver Soehnlein, Miriam MeradArthur Mortha, Lai Guan Ng, Hector Peinado, Andrés Hidalgo

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

Immune protection relies on the capacity of neutrophils to infiltrate challenged tissues. Naive tissues, in contrast, are believed to remain free of these cells and protected from their toxic cargo. Here, we show that neutrophils are endowed with the capacity to infiltrate multiple tissues in the steady-state, a process that follows tissue-specific dynamics. By focusing in two particular tissues, the intestine and the lungs, we find that neutrophils infiltrating the intestine are engulfed by resident macrophages, resulting in repression of Il23 transcription, reduced G-CSF in plasma, and reinforced activity of distant bone marrow niches. In contrast, diurnal accumulation of neutrophils within the pulmonary vasculature influenced circadian transcription in the lungs. Neutrophil-influenced transcripts in this organ were associated with carcinogenesis and migration. Consistently, we found that neutrophils dictated the diurnal patterns of lung invasion by melanoma cells. Homeostatic infiltration of tissues unveils a facet of neutrophil biology that supports organ function, but can also instigate pathological states.

Original languageEnglish
Pages (from-to)2778-2795
Number of pages18
JournalJournal of Experimental Medicine
Volume215
Issue number11
DOIs
StatePublished - 1 Nov 2018

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