Research Paper Title

Cadmium-induced immunosuppression
through TLR-IκBα-NFκB signaling by
promoting autophagic degradation
Presented by: Samia Akhtar
Class: MS Bioinformatics
Roll No: 2220851
Background
Cadmium (Cd) is a toxic heavy metal that poses a serious threat to
human health. It is widely spread in contaminated air, drinking water,
food, and various products.
Cd exposure can lead to immunosuppression, affecting the immune
system's ability to respond to infections.
The spleen plays an important role in the host immune system.
Cd exposure can accumulate in the spleen and cause apoptosis of
spleen tissue in mice.
Background (Cont..)
Autophagy is a process that can be promoted or inhibited by Cd
exposure and plays a role in systemic light chain plasma cells and
amyloidosis, as well as being an important component of innate
immunity.
Cd exposure can alter the immune system process and affect the
NFκB signaling pathway
Cd exposure can suppress the immune response by promoting the
autophagy-lysosomal degradation of toll-like receptor 9 (TLR9).
Abstract
Cd exposure poses a serious threat to human health and can perturb
the immune system, increasing the risk of pathogenicity and mortality
of infections.
The underlying mechanism of Cd-modulated immune responses
remains unclear.
This study aimed to investigate the role of Cd in the immune function
of mouse spleen tissues and its primary T cells under ConA activation
condition.
Cd exposure inhibited the expressions of TNF-α and IFN-γ in mouse
spleen tissues.
Abstract ( Cont..)
Cd exposure altered the immune system process and may affect the
NFκB signaling pathway.
Cd exposure reduced ConA-activated TLR9-IκBα-NFκB signaling
and the expressions of TLR9, TNF-α, and IFN-γ.
Autophagy-lysosomal inhibitors effectively reversed the Cd-induced
suppression of the immune response.
This study provides insight into the mechanism of Cd immunotoxicity
and its impact on immune responses.
Introduction
Cadmium (Cd) is a toxic heavy metal that poses a serious threat to
human health, and it is widely spread in contaminated air, drinking
water, food, and various products.
Cd exposure can lead to immunosuppression and increase the risk of
pathogenicity and mortality of infections.
The spleen plays an important role in the host immune system and is
considered an organ for studying Cd-induced immunotoxicity.
Cd exposure can accumulate in the spleen and cause apoptosis of
spleen tissue in mice.
Introduction (Cont..)
Previous studies have reported that Cd exposure can alter the
expression of immune-related genes in rat spleen and chicken splenic
lymphocytes.
The molecular mechanism underlying Cd-induced immunotoxicity is
still unclear, and there are conflicting results regarding the immune
response to Cd in different models.
Understanding the mechanisms of Cd-induced immunotoxicity and
abnormal immune responses in spleens is important for preventing Cd
toxicity and improving treatment outcomes in Cd-exposed individuals.
Research Objectives
Investigate the role of Cd in the immune function of mouse spleen
tissues and primary T cells under ConA activation condition
Elucidate the molecular mechanism of Cd-modulated immune
responses
Determine the effects of Cd exposure on the expressions of TNF-α
and IFN-γ in mouse spleen tissues
Understand the impact of Cd exposure on the immune system process
and the NFκB signaling pathway
Contribute to the understanding of the mechanisms of Cd-induced
immunotoxicity
Methodology
Mouse spleen tissues and primary T cells were used to investigate the role of
Cd in immune function under ConA activation condition.
The expressions of TNF-α and IFN-γ in mouse spleen tissues were measured
to assess the effects of Cd exposure.
Transcriptomic profiling using RNA-sequence analysis was performed to
identify Cd-induced alterations in the immune system process and NFκB
signaling pathway.
The impact of Cd exposure on toll-like receptor 9 (TLR9)-IκBα-NFκB
signaling and the expressions of TLR9, TNF-α, and IFN-γ were examined.
Autophagy-lysosomal inhibitors were used to determine the reversibility of
Cd-induced immunosuppression.
Results
• (A, B) Cd exposure time and
dosage on the mRNA levels.
• (C, D) Effects of Cd exposure on
the protein level.
• (F) Effects of Cd exposure on the
expression of apoptosis.
• (G) Quantification of the relative
protein levels.
Results
GO enrichment analysis of the
differentially expressed unigenes (DEGs)
in the ConA + Cd treated vs. ConA groups.
The lower x-axis indicates the number of
genes annotated to a certain GO term, and
the upper x-axis indicates the ratio of the
number of genes annotated to a certain GO
term to the total number of all GO
annotation genes; the y-axis indicates each
detailed classification of GO. The red bar
represents the up-regulated gene and the
blue bar represents the down-regulated
gene.
Results
• (A)TOP 20 of KEGG pathway
enrichment of special DEGs between
ConA + Cd vs. ConA group.
• (B)Western blotting analysis of IκBα-
NFκB signaling and TLR2, TLR4,
and TLR9 expressions in primary
mouse spleen T cells after Cd
exposure under the ConA activation
condition.
• (C, D) Quantification of the relative
protein levels was performed by
using the software Image.
Results
• (A) Immunohistochemistry
detection.
• (B, D)Quantification of the
fluorescence intensity.
• (C) Western blotting of the
expressions.
• (E) RT-qPCR.
• (F) ELISA assay
Conclusion
Cd exposure induces immunosuppression by inhibiting the expressions
of TNF-α and IFN-γ in mouse spleen tissues
Cd exposure alters the immune system process and affects the NFκB
signaling pathway.
Cd exposure suppresses immune response under ConA activation
condition by promoting the autophagy-lysosomal degradation of TLR9.
Autophagy-lysosomal inhibitors effectively reverse Cd-induced
immunosuppression.
Mechanism of Cd immunotoxicity and suggests potential strategies for
preventing Cd toxicity in the future.
Study Gap
The molecular mechanism of Cd-modulated immune responses
remains unclear.
Previous studies have shown that Cd exposure can cause abnormal
immune responses, but the specific molecular mechanism is still
unknown.