Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice.

Sílvia Pires,Davida S Smyth,Adeline Peignier,Dane Parker,Jeremy Seto

doi:10.1172/jci.insight.132223

Abstract

Acinetobacter baumannii (A. baumannii) is an extremely versatile multidrug-resistant pathogen with a very high mortality rate; therefore, it has become crucial to understand the host response during its infection. Given the importance of mice for modeling infection and their role in preclinical drug development, equal emphasis should be placed on the use of both sexes. Through our studies using a murine model of acute pneumonia with A. baumannii, we observed that female mice were more susceptible to infection. Likewise, treatment of male mice with estradiol increased their susceptibility to infection. Analysis of the airway compartment revealed enhanced inflammation and reduced neutrophil and alveolar macrophage numbers compared with male mice. Depletion of either neutrophils or alveolar macrophages was important for bacterial clearance; however, depletion of alveolar macrophages further exacerbated female susceptibility because of severe alterations in metabolic homeostasis. Our data highlight the importance of using both sexes when assessing host immune pathways.

Highlights

Acinetobacter baumannii (A. baumannii) is an emerging opportunistic and extremely versatile multidrug-resistant pathogen that has become a serious global threat, resulting in high mortality rates [1, 2]
Our data highlight the importance of using both sexes when assessing host immune pathways to A. baumannii and point to a crucial metabolic role for alveolar macrophages in controlling infection in female mice
We demonstrated that the differential susceptibility to A. baumannii–induced pneumonia between sexes is based on altered immune cell populations in the airway, neutrophils, and depletion of alveolar macrophages leads to a metabolic impairment of female mice following infection, hindering their capacity to combat infection

Summary

Introduction

Acinetobacter baumannii (A. baumannii) is an emerging opportunistic and extremely versatile multidrug-resistant pathogen that has become a serious global threat, resulting in high mortality rates [1, 2]. Its extreme genome plasticity and ability to quickly develop resistance to a plethora of antibiotics makes it an important pathogen and one of the reasons it has been designated as a serious threat and critical target by the CDC and World Health Organization [3,4,5,6,7]. This has driven significant research in recent years to understand how the host senses and responds to A. baumannii infection [8, 9]. Our data highlight the importance of using both sexes when assessing host immune pathways to A. baumannii and point to a crucial metabolic role for alveolar macrophages in controlling infection in female mice

Methods

Results

Conclusion