Zinc deficiency is associated with an increased risk of lung infection

Dietary zinc deficiency promotes lung infection by the bacteria Acinetobacter baumannii — a leading cause of ventilator-associated pneumonia, according to a new study published Nov. 15 in the journal Nature Microbiology.

A team of researchers led by Vanderbilt University Medical Center discovered an unexpected link between the pro-inflammatory cytokine interleukin-13 (IL-13) and A. baumannii lung infection and demonstrated that blocking IL-13 prevented death associated with the infection animal model.

The findings suggest that anti-IL-13 antibodies, which are FDA-approved for use in humans, may protect against bacterial pneumonia in zinc-deficient patients.

To our knowledge, this is the first study to show that neutralizing IL-13 could prevent mortality from bacterial infection. This discovery indicates the potential for using anti-IL-13 therapy in patients with zinc deficiency and A. baumannii pneumonia as part of an individualized treatment approach.”

Eric Skaar, PhD, MPH, the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology and Inflammation

Nearly 20% of the world’s population is at risk of zinc deficiency, which can impair immune function and is a major risk factor for pneumonia. The World Health Organization considers zinc deficiency to be the leading cause of disease and death.

Patients at risk for zinc deficiency, particularly critically ill and elderly patients, are also at risk for A. baumannii infection. Patients in health care settings are at the highest risk of infection, especially those who are on ventilators, have devices such as catheters, are in intensive care units, or have prolonged hospital stays. A. baumannii is becoming increasingly resistant to antimicrobial treatments, making it a critical threat to public health, Skaar said.

To investigate whether and how dietary zinc deficiency contributes to A. baumannii pathogenesis, researchers established a murine model of dietary zinc deficiency and acute A. baumannii pneumonia. Lauren Palmer, PhD, a former postdoctoral fellow at VUMC who is now an assistant professor of microbiology and immunology at the University of Illinois at Chicago, led the studies.

The researchers found that zinc-deficient mice had increased A. baumannii bacterial burden in the lungs, spread of bacteria in the spleen, and higher mortality compared to mice with adequate dietary zinc consumption. They showed that zinc-deficient mice produced more IL-13 during infection and that administration of IL-13 to zinc-sufficient mice promoted the spread of A. baumannii in the spleen. Anti-IL-13 antibody treatment protected zinc-deficient mice from death caused by A. baumannii.

The findings add to a growing body of studies showing that certain nutrient deficiencies are associated with IL-13 production and a “type 2” immune response.

“IL-13 may be an important risk factor for healthcare-associated and opportunistic lung infections, further supporting the exploration of IL-13 as a therapeutic target,” Skaar noted.

The FDA-approved anti-IL-13 antibodies (lebricizumab and tralokinumab) have been extensively investigated as potential treatments for uncontrolled severe asthma. Although not found to be effective for this indication, clinical trials have demonstrated their safety.

Palmer is first and co-corresponding author with Skaar Nature Microbiology report. Other authors are Zachery Lonergan, PhD, Dziedzom Bansah, Xiaomei Ren, PhD, Lillian Juttukonda, MD, PhD, Christopher Pinelli, DVM, PhD, and Kelli Boyd, DVM, PhD. The research was supported in part by the National Institutes of Health (grants R01AI101171, R01AI017829, F31AI136255, T32HL094296, F32AI122516, K99HL143441, R00HL1430440, R00HL14304405).