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Macrophages Maintain Epithelial Barrier Integrity in the Distal Colon by Limiting the Absorption of Fluids Containing Fungal Products

57 Pages Posted: 8 May 2020 Sneak Peek Status: Under Review

See all articles by Aleksandra Chikina

Aleksandra Chikina

Institut Curie - Immunity & Cancer

Francesca Nadalin

PSL Research University - Institut Curie

Mathieu Maurin

Institut Curie - Immunity & Cancer

Mabel San-Roman

PSL Research University - Institut Curie

Thibault Thomas-Bonafos

PSL Research University - Institut Curie

Xin V. Li

Cornell University

Sonia Lameiras

Institut Curie - Next generation Sequencing facility

Sylvain Baulande

Institut Curie - Next generation Sequencing facility

Sandrine Henri

Aix-Marseille University

Bernard Malissen

Aix-Marseille University

J. Magarian Blander

Cornell University

Iliyan D. Iliev

Cornell University

Danijela Matic Vignjevic

PSL Research University - Institut Curie

Ana-Maria Lennon-Duménil

Institut Curie - Immunity & Cancer

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Abstract

The colon is responsible for absorbing fluids. It contains many microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must thus tightly regulate fluid influx to avoid absorption of fungal metabolites, which can be toxic to epithelial cells and reach the blood circulation, leading to barrier dysfunction and sepsis. How this is achieved remains unknown. Here, we describe a mechanism by which macrophages rapidly check the fluids absorbed through epithelial cells to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages equipped with "balloon-like" protrusions (BLPs) inserted at the base of epithelial cells. BLPs sample absorbed fluids and stop absorption when fluids contain fungal toxins. Without macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to apoptosis and loss of epithelium integrity. These results reveal an unexpected role of macrophages in the maintenance of colon-microbiota interactions in homeostasis.

Keywords: macrophages, gut, epithelium integrity, microbiota, fluid absorption, protrusions

Suggested Citation

Chikina, Aleksandra and Nadalin, Francesca and Maurin, Mathieu and San-Roman, Mabel and Thomas-Bonafos, Thibault and Li, Xin V. and Lameiras, Sonia and Baulande, Sylvain and Henri, Sandrine and Malissen, Bernard and Blander, J. Magarian and Iliev, Iliyan D. and Vignjevic, Danijela Matic and Lennon-Duménil, Ana-Maria, Macrophages Maintain Epithelial Barrier Integrity in the Distal Colon by Limiting the Absorption of Fluids Containing Fungal Products. Available at SSRN: https://ssrn.com/abstract=3582693 or http://dx.doi.org/10.2139/ssrn.3582693
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Aleksandra Chikina

Institut Curie - Immunity & Cancer ( email )

France

Francesca Nadalin

PSL Research University - Institut Curie

France

Mathieu Maurin

Institut Curie - Immunity & Cancer

France

Mabel San-Roman

PSL Research University - Institut Curie

France

Thibault Thomas-Bonafos

PSL Research University - Institut Curie

France

Xin V. Li

Cornell University

Ithaca, NY 14853
United States

Sonia Lameiras

Institut Curie - Next generation Sequencing facility ( email )

France

Sylvain Baulande

Institut Curie - Next generation Sequencing facility ( email )

France

Sandrine Henri

Aix-Marseille University

3 Avenue Robert Schuman
3 Avenue Robert Schuman,
Aix-en-Provence, 13628
France

Bernard Malissen

Aix-Marseille University ( email )

3 Avenue Robert Schuman
3 Avenue Robert Schuman,
Aix-en-Provence, 13628
France

J. Magarian Blander

Cornell University

Ithaca, NY 14853
United States

Iliyan D. Iliev

Cornell University

Ithaca, NY 14853
United States

Danijela Matic Vignjevic

PSL Research University - Institut Curie ( email )

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Ana-Maria Lennon-Duménil (Contact Author)

Institut Curie - Immunity & Cancer ( email )

France

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