Sex differences in the C57BL/6 model of Mycobacterium tuberculosis infection

Dibbern, Jannike; Eggers, Lars; Schneider, Bianca E.

doi:10.1038/s41598-017-11438-z

Cited by 50 publications

(52 citation statements)

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“…Our observations in H37Rv infected C57BL/6 mice pointed to an impaired formation of lymphoid aggregates in the male lung 6 . In the current study, we substantiate our previous observation and show that B cell follicles that form in the Mtb infected lung were much smaller in males compared to females.…”

Section: David Hertz Jannike Dibbern Lars Eggers Linda Von Borstelsupporting

confidence: 60%

“…Of note, IL-23 was significantly reduced in males shortly before their condition began to deteriorate (Fig. 1B) 6 . In good agreement, the expression of CXCL13 was significantly lower in male compared to female lungs at the same time point (Fig.…”

Section: Resultsmentioning

confidence: 91%

“…Mtb H37Rv infection in males is associated with smaller B cell follicles. We previously showed that a reduced resistance of male C57BL/6 mice to aerosol infection with H37Rv was associated with smaller lymphoid aggregates in the infected lung 6 . Immunohistochemical evaluation of lung sections revealed that lymphoid aggregates are rich in B220 positive B cells ( Fig.…”

Section: Resultsmentioning

confidence: 98%

“…Next to socioeconomic and cultural factors, the biological sex significantly contributes to differences between the sexes in infectious diseases. We have previously shown that male C57BL/6 mice are more susceptible to H37Rv infection 6 . Together with the data presented here our observations in H37Rv-infected C57BL/6 mice point to an impaired formation of ELS in the male lung.…”

Section: Discussionmentioning

confidence: 98%

“…For infection of experimental animals, Mtb stocks were diluted in sterile distilled water at a concentration providing an uptake of 100 viable bacilli per lung. Infection was performed via the respiratory route by using an aerosol chamber (Glas-Col) as described previously 6 . The uptake was quantified 24 h after infection by determining CFU in the lungs of infected mice.…”

Section: David Hertz Jannike Dibbern Lars Eggers Linda Von Borstelmentioning

confidence: 99%

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Increased male susceptibility to Mycobacterium tuberculosis infection is associated with smaller B cell follicles in the lungs

Hertz

Dibbern

Eggers

et al. 2020

Sci Rep

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Tuberculosis prevalence is significantly higher among men than women. We have previously revealed an increased susceptibility of male C57BL/6 mice towards Mycobacterium tuberculosis (Mtb) H37Rv. In the current study, we confirm the male bias for infection with the Beijing strain HN878. Males succumbed to HN878 infection significantly earlier than females. In both models, premature death of males was associated with smaller B cell follicles in the lungs. Analysis of homeostatic chemokines and their receptors revealed differences between H37Rv and HN878 infected animals, indicating different immune requirements for follicle formation in both models. However, expression of IL-23, which is involved in long-term containment of Mtb and lymphoid follicle formation, was reduced in male compared to female lungs in both models. Our study reveals sex differences in the formation of B cell follicles in the Mtb infected lung and we propose that impaired follicle formation is responsible for accelerated disease progression in males.Tuberculosis (TB) is the most prevalent bacterial infectious disease in humans. The causative agent, Mycobacterium tuberculosis (Mtb), is carried by an estimated 2-3 billion people globally and claims approximately 1.5 million lives each year 1 . The global TB pandemic is characterized by significant differences in prevalence between men and women, reflected by a male-to-female ratio for worldwide case notifications of 1.8 1 . Both gender-and sex-related factors likely contribute to higher TB rates in men, but the role of the latter has been largely ignored 2-5 .We have previously shown an increased susceptibility for male C57BL/6 mice to infection with the laboratory-adapted strain Mtb H37Rv 6 . Accelerated disease progression in males after low-dose aerosol infection resulted in increased morbidity and mortality compared to females. Likewise, a study in BALB/c mice revealed that males are more susceptible to H37Rv infection than females 7 . The fact that two of the most widely used TB mouse models do reflect the global male bias in humans emphasizes the need to include both sexes in basic research and pre-clinical studies.Our observations in H37Rv infected C57BL/6 mice pointed to an impaired formation of lymphoid aggregates in the male lung 6 . In the current study, we substantiate our previous observation and show that B cell follicles that form in the Mtb infected lung were much smaller in males compared to females. Moreover, expression of chemokines associated with the homing of lymphocytes to the infected lung such as CXCL13 and CCL19 was significantly lower in males compared to females, further indicating that B cell follicle formation in response to H37Rv infection is impaired in males.Mtb is a member of the Mtb complex (Mtbc), and Mtbc strains are more genetically diverse than was previously recognized 8 . Importantly, genetic diversity might contribute to clinical, pathogenic, and immunologic heterogeneity in disease progression and outcome. H37Rv was isolated in 1905 and is not a relevant...

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Section: David Hertz Jannike Dibbern Lars Eggers Linda Von Borstelsupporting

confidence: 60%

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Section: David Hertz Jannike Dibbern Lars Eggers Linda Von Borstelmentioning

confidence: 99%

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