Neutrophil Fast Squad Are First Responders to Bacterial Lung Invaders

The body's usual response to a bacterial infection in the blood — called sepsis — takes time. It requires a carefully orchestrated sequence of events that gets the body's immune system ramped up to deal with the invading bacteria.

A type of white blood cells called macrophages that hang out in the liver and spleen are the cells usually responsible for finding, engulfing, and eliminating bacteria that flows by in the blood. But not all bacteria can be found flowing through major blood vessels of the body. Some escape macrophage detection by sneaking into smaller pockets of the circulatory system, like the tiny capillaries of the lung.

Blood vessels in the lungs get progressively smaller the deeper into the lungs they travel, until they end in one-cell-thick capillary vessels that surround the air sacs of the lung where oxygen passes from the air in the lungs into the blood.

When researcher Bryan Yipp from the University of Calgary in Alberta, Canada, as well as his colleagues in the study, observed a sharp drop in immune cells — white blood cells called neutrophils — in the blood of healthy people exposed to toxins from bacteria, they went in search of the missing neutrophils.

They labeled the neutrophils of mice with a green fluorescent dye, then infected the mice with Escherichia coli. The green dye allowed the scientists to easily see where the neutrophils went in response to the blood infection.

The study authors found the mouse neutrophils crawling along the walls of the tiny lung capillaries, looking for the bacteria hiding there. The movement of neutrophils to the capillaries happened within minutes of exposure to the bacteria.

Neutrophils (green) crawling in the lung vessels (red), seeking out microbes that are "hiding" from immune cells.

In another experiment where the scientists labeled the neutrophils blue and the bacteria red, they observed the neutrophils crawling to and rapidly gobbling up the E. coli in a process called phagocytosis. In phagocytosis, immune cells ingest the bacteria, then digest it to destroy it.

Neutrophils (blue) capture bacteria (red) in lung capillaries.

The presence of lipopolysaccharides — fats and sugars — that make up bacteria cell walls is one of the main alerts to the immune system that they need to react to bacteria.

Lipopolysaccharides trigger cell signals that recruit more immune cells and release chemicals like cytokines and proteins that work together to kill the bacteria. That cascade of activity takes time, though — precious hours when the infection is taking hold unchallenged.

Acting quickly after bacterial invasion, neutrophils accumulate in the lung vasculature, seeking out and eliminating “hidden” microbes.

The study authors noted that lipopolysaccharides can also increase molecules on the surface of neutrophils that help them stick to the cells lining capillaries, assisting them in binding to and traveling along the vessel to locate the hidden bacteria. And this process can occur within minutes.

The research by Yipp and colleagues discovered a new process where cells lining capillaries and neutrophils work together to form a rapid response team that cooperates to provide almost immediate detection and capture of pathogens hiding out in the farthest reaches of our blood vessels.

It's a process that can help us get on top of bacterial sepsis during the precious time interval before our full immune system kicks in and before the infection gets out of control.

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Cover image via Patrick J. Lynch/Wikimedia Commons