Untersuchung zur Bedeutung des Mikrobioms bei Infektionen mit Streptococcus pneumoniae im Alter
Immunologie
Zusammenfassung der Projektergebnisse
With age the immune system changes dramatically and therefore our ability to fight infections changes considerably. These changes perturb the delicate balance between inflammatory and antiinflammatory networks, resulting in a low grade chronic pro-inflammatory status of the whole organism. However, it is not resolved yet what causes these changes. Analyses in humans comparing the composition of the microbiota in young adults and elderly detected severe differences and studies in mice addressing this question showed that old germ-free mice do not show an age-related decline in immune function. The aim of this project was to analyze how the composition of the microbiota influences the immune status and what causes the decline of immune function found in the elderly. Therefore, in this study I investigated the effect of the aging microbiome in C57Bl/6 mice on immune function and the permissiveness against colonization with Streptococcus pneumoniae in relation to sex, frailty and other parameters. Two groups of mice would be observed. The first group consisted of 25 females and 25 males, who were kept under standardized living conditions for two years. In the second year of life, the changes that entailed the age were determined. In general, the mice aged very individually despite the same life background. There were significant differences between the females and the males. Also, certain signs of aging in some mice occurred much earlier than expected. The second study group consisted of young (<5months) and old germ-free mice (>18months) were recolonized with microbiota from young or old SPF mice within 6 weeks. Before and after colonization, the immune status was documented to detect changes in the immune system after recolonization. The limited availability of old germ-free mice resulted in high diverse outcomes in very small groups. The original germ-free mice and now recolonized with a “young” or “old” microbiome were administered nasally with a small doses of S. pneumoniae. After 5 days, the bacterial load of pneumococci was determined in nasal lavage of the mice. It was found that old male mice with an “old” transferred microbiome were more susceptible to colonization with pneumococci than mice with a “young” microbiome. Numerous factors play a role such as age, genetic background, microbiome, BMI, diet, and sex hormones for changes of the immune system. This makes it difficult to differentiate the causes. That's why mechanisms and reasons behind the different rates of aging as well as dimorphic responses are still incompletely understood. In the future it will be necessary to increase the number of mice in the SPF as well as in the germ-free group in order to cope with the high diversity and to identify subgroups of old mice distinct from other old mice by their sex, immune status, microbiome and fitness.
Projektbezogene Publikationen (Auswahl)
- (2017) Age‐Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Cell Host & Microbe. 21(4), 455 – 466
Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JD, Larché MJ, Davidson DJ, Verdú EF, Surette MG, Bowdish DME
(Siehe online unter https://doi.org/10.1016/j.chom.2017.03.002) - (2018) TNF, but not hyperinsulinemia or hyperglycemia, is a key driver of obesity‐induced monocytosis revealing that inflammatory monocytes correlate with insulin in obese male mice. Physiol Rep. 6(23)
Breznik JA, Naidoo A, Foley KP, Schulz C, Lau TC, Loukov D, Sloboda DM, Bowdish DME, Schertzer JD
(Siehe online unter https://doi.org/10.14814/phy2.13937)
