Differential Susceptibility of Male Versus Female Laboratory Mice to Anaplasma phagocytophilum Infection

Abstract

Human granulocytic anaplasmosis (HGA) is a debilitating, non-specific febrile illness caused by the granulocytotropic obligate intracellular bacterium called Anaplasma phagocytophilum. Surveillance studies indicate a higher prevalence of HGA in male versus female patients. Whether this discrepancy correlates with differential susceptibility of males and females to A. phagocytophilum infection is unknown. Laboratory mice have long been used to study granulocytic anaplasmosis. Yet, sex as a biological variable (SABV) in this model has not been evaluated. In this paper, groups of male and female C57Bl/6 mice that had been infected with A. phagocytophilum were assessed for the bacterial DNA load in the peripheral blood, the percentage of neutrophils harboring bacterial inclusions called morulae, and splenomegaly. Infected male mice exhibited as much as a 1.85-fold increase in the number of infected neutrophils, which is up to a 1.88-fold increase in the A. phagocytophilum DNA load, and a significant increase in spleen size when compared to infected female mice. The propensity of male mice to develop a higher level of A. phagocytophilum infection is relevant for studies utilizing the mouse model. This stresses the importance of including SABV and aligns with the observed higher incidence of infection in male versus female patients.

Analysis of epidemiological characteristics of four natural-focal diseases in Shandong Province, China in 2009-2017: A descriptive analysis

“…Two factors may account for the result- the increased proportion of females engaging in outdoor activities [39], and the higher susceptibility of females to O . tsutsugamushi compared with males [40] which may require further investigation and experimentation.…”

Analysis on epidemiological characteristics of 4 species natural-focal diseases in Shandong Province, China in 2009-2017: a descriptive analysis

“…First, the increased proportion of females engaging in outdoor activities[38]. Second, female may be more susceptible to Orientia tsutsugamushi than males[39]. This requires further experimentation to explore.…”

Binding of Host Cell Surface Protein Disulfide Isomerase by Anaplasma phagocytophilum Asp14 Enables Pathogen Infection

“…The generation and breeding of myeloid-specific-PDI conditional-knockout (PDI CKO) CKO mice have been described previously (25). Six-to 12-week-old PDI CKO or age-and sex-matched C57BL/6 control mice (Jackson Laboratories, Bar Harbor, ME) were intraperitoneally inoculated with 1 ϫ 10 8 A. phagocytophilum DC organisms (39). Quantification of the peripheral blood A. phagocytophilum burden was determined as described previously (39).…”

“…Six-to 12-week-old PDI CKO or age-and sex-matched C57BL/6 control mice (Jackson Laboratories, Bar Harbor, ME) were intraperitoneally inoculated with 1 ϫ 10 8 A. phagocytophilum DC organisms (39). Quantification of the peripheral blood A. phagocytophilum burden was determined as described previously (39). All animal research was performed under the approval of the Institutional Animal Care and Use Committee at Virginia Commonwealth University (protocol number AM10220).…”