Sex differences in Health and Disease
(2023) KIMM05 20231Department of Immunotechnology
- Abstract
- Sexual dimorphism in the immune system plays a crucial role in disease susceptibility and pathogenesis, yet it is often overlooked in medical and research fields. This study aims to address this knowledge gap by investigating sex differences in immunity at an unstimulated baseline state and in response to Mycobacterium tuberculosis (MTB) stimulation using an in-silico approach. By analyzing single-cell RNA sequencing data from healthy human peripheral blood mononuclear cells (PBMCs), we identified sex differences in cellular composition and gene expression. Our results reveal that males exhibit a higher frequency of innate immune cells, while females show a higher frequency of adaptive immune cells. We also found that both age and sex... (More)
- Sexual dimorphism in the immune system plays a crucial role in disease susceptibility and pathogenesis, yet it is often overlooked in medical and research fields. This study aims to address this knowledge gap by investigating sex differences in immunity at an unstimulated baseline state and in response to Mycobacterium tuberculosis (MTB) stimulation using an in-silico approach. By analyzing single-cell RNA sequencing data from healthy human peripheral blood mononuclear cells (PBMCs), we identified sex differences in cellular composition and gene expression. Our results reveal that males exhibit a higher frequency of innate immune cells, while females show a higher frequency of adaptive immune cells. We also found that both age and sex hormones significantly impact the sexual dimorphism in cellular composition. Furthermore, our cell-to-cell communication analysis highlights the interplay between innate and adaptive immune cells, with males demonstrating a correlation between these cell types, while females exhibit a stronger correlation between CD4+ and CD8+ T cells. Moreover, our analysis of gene expression patterns indicates that male immune cells display a more pronounced inflammatory response, whereas females exhibit higher expression of genes involved in ribosomal pathways and the extracellular matrix. These findings provide valuable insights into the mechanisms contributing to sex-specific immune responses and may help explain the observed sex bias in tuberculosis outcomes. Analysis of in vitro stimulated innate cells revealed a stronger upregulation on inflammatory pathways in males when compared to females with the genes MMP-1 and CXCL9 overexpressed in males. Understanding these observed sex differences is crucial for the development of tailored treatments more suited to a patient’s sex. Additionally, our findings are important for other respiratory tract infections, emphasizing the importance of the delicate balance between inflammation and extracellular matrix integrity in lung diseases. By shedding light on the intricate relationship between sexual dimorphism and immune responses, this research paves the way for future investigations into sex-specific therapeutic interventions in infectious diseases. (Less)
- Popular Abstract
- This study explores the fascinating world of the human immune system and aims to understand why some people are more severely affected by certain diseases than others. We specifically focus on the differences between males and females in disease susceptibility. For example, males tend to suffer more from infections like COVID-19 and tuberculosis, as well as most cancers. On the other hand, females may experience more negative side effects from vaccines and have a higher risk of immune diseases such as multiple sclerosis.
In our research, we examined tuberculosis, a disease caused by a bacterium called Mycobacterium tuberculosis, which affects the lungs. Tuberculosis claims millions of lives annually and affects males more severely. Our... (More) - This study explores the fascinating world of the human immune system and aims to understand why some people are more severely affected by certain diseases than others. We specifically focus on the differences between males and females in disease susceptibility. For example, males tend to suffer more from infections like COVID-19 and tuberculosis, as well as most cancers. On the other hand, females may experience more negative side effects from vaccines and have a higher risk of immune diseases such as multiple sclerosis.
In our research, we examined tuberculosis, a disease caused by a bacterium called Mycobacterium tuberculosis, which affects the lungs. Tuberculosis claims millions of lives annually and affects males more severely. Our findings suggest that one reason for this disparity lies in the strength of the innate immune system, which is the body's initial defense against bacteria. Males are observed to mount a stronger innate immune response, but this comes with the consequence of excessive inflammation which can harm the body. In contrast, females exhibit a better adaptive immune response, which helps fight infections over the long term. The adaptive response is intelligent and precise, effectively aiding the body in combating harmful pathogens.
Understanding these differences in how males and females respond to infections will ultimately assist in developing treatments that are better suited to an individual's sex. By considering these sex-based immune variations, significant progress can be made towards a more personalized healthcare. For further details about this research, you can refer to the original degree project titled "Sex Differences in Health and Disease" by Andrea Sonnenholzner. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9129452
- author
- Sonnenholzner, Andrea LU
- supervisor
- organization
- course
- KIMM05 20231
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9129452
- date added to LUP
- 2023-06-26 11:44:41
- date last changed
- 2023-06-26 11:44:41
@misc{9129452,
abstract = {{Sexual dimorphism in the immune system plays a crucial role in disease susceptibility and pathogenesis, yet it is often overlooked in medical and research fields. This study aims to address this knowledge gap by investigating sex differences in immunity at an unstimulated baseline state and in response to Mycobacterium tuberculosis (MTB) stimulation using an in-silico approach. By analyzing single-cell RNA sequencing data from healthy human peripheral blood mononuclear cells (PBMCs), we identified sex differences in cellular composition and gene expression. Our results reveal that males exhibit a higher frequency of innate immune cells, while females show a higher frequency of adaptive immune cells. We also found that both age and sex hormones significantly impact the sexual dimorphism in cellular composition. Furthermore, our cell-to-cell communication analysis highlights the interplay between innate and adaptive immune cells, with males demonstrating a correlation between these cell types, while females exhibit a stronger correlation between CD4+ and CD8+ T cells. Moreover, our analysis of gene expression patterns indicates that male immune cells display a more pronounced inflammatory response, whereas females exhibit higher expression of genes involved in ribosomal pathways and the extracellular matrix. These findings provide valuable insights into the mechanisms contributing to sex-specific immune responses and may help explain the observed sex bias in tuberculosis outcomes. Analysis of in vitro stimulated innate cells revealed a stronger upregulation on inflammatory pathways in males when compared to females with the genes MMP-1 and CXCL9 overexpressed in males. Understanding these observed sex differences is crucial for the development of tailored treatments more suited to a patient’s sex. Additionally, our findings are important for other respiratory tract infections, emphasizing the importance of the delicate balance between inflammation and extracellular matrix integrity in lung diseases. By shedding light on the intricate relationship between sexual dimorphism and immune responses, this research paves the way for future investigations into sex-specific therapeutic interventions in infectious diseases.}},
author = {{Sonnenholzner, Andrea}},
language = {{eng}},
note = {{Student Paper}},
title = {{Sex differences in Health and Disease}},
year = {{2023}},
}