Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice
Sílvia Pires, … , Davida S. Smyth, Dane Parker
Sílvia Pires, … , Davida S. Smyth, Dane Parker
Published March 19, 2020
Citation Information: JCI Insight. 2020;5(7):e132223. https://doi.org/10.1172/jci.insight.132223.
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Research Article Immunology Infectious disease

Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice

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.

Authors

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

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Figure 1

Female mice are more susceptible to pulmonary A. baumannii infection.

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Female mice are more susceptible to pulmonary A. baumannii infection. (...
(A) Weights of mice before infection. (B) Mice were intranasally infected with 108 CFU of A. baumannii 5075 and mortality was assessed (n = 26 female; n = 8 male). (C–E) Weight-matched female and male C57BL/6J WT mice were intranasally infected with 107 CFU of A. baumannii 5075 for 24 hours (n = 12). (C) BALF, lung, and spleen homogenates were enumerated for bacterial counts 24 hours after infection (n = 9). (D) Change in external temperature of female and male mice 24 hours after intranasal infection. (E) Protein content in BALF. n = 4 and n = 5 for uninfected female and male mice, respectively. (F) Representative H&E-stained lung sections of mice at 24 hours after infection. Scale bars: 1 mm (left), 100 μm (right). (G and H) Male mice were treated with 17β-estradiol or vehicle control for 5 days prior to intranasal infection with 107 CFU of A. baumannii 5075 (n = 11). (G) BALF, lung, and spleen homogenates were enumerated for bacterial counts 24 hours after infection. (H) Change in external temperature of mice after infection (n = 12). Each point represents a mouse. Lines display means with SEM. Data are from 3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Mortality data were assessed using Fisher’s exact test. A nonparametric Mann-Whitney U test was used to assess differences between groups.