Streptococcus pyogenes is a Group A Streptoccocal (GAS) bacterium that causes a
ID: 189250 • Letter: S
Question
Streptococcus pyogenes is a Group A Streptoccocal (GAS) bacterium that causes a variety of diseases depending on the tissue that is infected. Most frequently, this bacterium causes strep throat and localized infections in the skin. Rarely, the bacteria spread to the blood causing a life-threatening infection with a mortality rate of ~25%. Studies of S. pyogenes infections in mouse models have shown that recruitment of neutrophils to the site(s) of infection is essential in the elimination of GAS infection. To further determine the innate immune pathways involved in protection from GAS, mice lacking the adapter protein MyD88 (MyD88-/- mice) were tested for their response to GAS compared with wild-type (WT, C57BL/6) control mice. The results are shown the survival curve below.
In a second experiment, another group of MyD88 -/- and WT mice were infected with an even higher dose of S. pyogenes. In the survival curve shown below (panel A), you can see that all the mice (even WT mice) eventually died from this severe infection. However, the average survival time of WT mice was significantly longer than for MyD88-/- mice. Measurements of bacterial counts in the blood within the first 24 hours post infection confirmed the poor innate immune response of the MyD88-/- mice (panel B).
a). Propose at least one explanation for the importance of MyD88 in the innate immune response to GAS that work with the data. Be sure to explain your reasoning.
b). If TLRs are not required for the innate immune response to GAS, what other sensor of bacterial components is a good candidate to induce the transcription of pro-inflammatory cytokine genes? Explain how this sensor pathway works (describe how it is activated, how the signal is transducted, and the outcomes)
100 C57BL/6 50 MyD88- 0 1 23 4 5 6 7 8 Time of infection (days)Explanation / Answer
Innate immune system defends the host from the infection; it creates immediate responds to infection and protects the host body. MyD88-/- mice do not have MyD88 gene. As shown in graph, when this mice is infected with GAS, in both case the mice will died within 2 days. Whereas wild type WT mice survive in non infection stage and died at 5th day on high infection dose of GAS. Additionally, CFU rate is high in case of MyD88-/- mouth after 24 hours which clearly indicates that the innate immune system is fail to protect mice from infection. Hence MYD88 gene important for signal transduction of innate immune system.
b.
when bacterial components as like cell wall (lipopolysaccharides) comes in contact with innate immune system cells, (if TLRs are absent) than CD14 induced pro inflammatory cytokines and activates innate immune sytem.
Inter lukins IL-1, IL-2, IL-18, TNF and INF-gamma are common type of cytokines involve in innate immunity.
When foreign pathogen comes in contact with host TLRs (or incase when TLRs are absent) CD14 receptors present on macrophage, activates the signal transduction process of innate immune system.
After that engulfted pathogen is recognized by the receptor (IL-1,2 or 18) which gives signal to T cells (native T cell) of adaptive immune system. During these process IL-1, IL-2, IL-18 and TNF like transcription factors play important role to switch on the expression. Finally it gives signal to B cell to produce antibodies specific to foreign antigen.
In the final stage, the antigen (foreign pathogen) binds to antibody where special receptor presents on microphage, recognize the antigen; antibody complex and finally destroys the foreign pathogen.