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Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice
Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker
Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker
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Research Article Immunology Infectious disease

Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice

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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 3

Depletion of alveolar macrophages results in a significantly higher bacterial burden in female than male infected mice.

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Depletion of alveolar macrophages results in a significantly higher bact...
(A) Representative flow cytometry contour plot showing neutrophils in BALF of mice that were treated with either α-IgG control or α-Ly6G, then infected intranasally with 107 CFU of A. baumannii. Neutrophils were identified as live CD45+SiglecF–MHCII–Ly6C+CD11b+. (B) Percentage of neutrophils in both female and male infected mice after neutrophil depletion relative to nondepleted levels. n = 6. (C) Fold induction of bacterial numbers 24 hours after infection in female and male mice that were depleted of neutrophils compared with nondepleted controls. n = 6. (D) Representative flow cytometry contour plot showing alveolar macrophages in BALF of mice treated with either liposome-only control or clodronate-loaded liposomes 24 hours prior to intranasal infection with 107 CFU of A. baumannii for 24 hours. Alveolar macrophages were identified as live CD45+Ly6C–CD11c+SiglecF+. (E) Percentage of alveolar macrophages in both female and male infected mice after alveolar macrophage depletion relative to nondepleted levels. n = 6. (F) Fold induction of bacterial numbers 24 hours after infection in female and male mice that were depleted of alveolar macrophages compared with nondepleted control. n = 5. (G) ROS levels in the airway of clodronate-treated female and male mice 24 hours after infection. n = 10. Graphs show means with SEM. Each point represents a mouse. Data are from at least 2 independent experiments. *P < 0.05, and **P < 0.01. A nonparametric Mann-Whitney U test was used to assess differences between groups.

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