Suzzana Buabeng Poster 2024

Ms Suzzana Buabeng

Stellenbosch University, South Africa

Assessment of the Pharmacological Modulation of the Acute and Chronic Immune Response to Mycobacterium tuberculosis Infection via the CaMK1δ Inhibitor CS0640 in a Diet-Induced Prediabetes Murine Model

Poster Abstract

Background
The comorbidity of tuberculosis (TB) and type 2 diabetes (T2D) has for many years threatened public health. T2D presents with dysregulated inflammatory responses that increase susceptibility to TB and propagate TB disease severity. The inhibition of the CaMK1 signalling pathway, which plays a major role in inflammation and endocrine responses, by the newly synthesized compound, CS0640 has been proven to enhance glucose control and insulin sensitivity in a dietinduced obesity murine model. However, CS0640 mediation of immune-endocrine response during the acute and chronic phases of M.tb infection in T2D hosts has not been studied. The current study therefore aims to assess the pharmacological modulation of the acute and chronic immune responses to M.tb via CS0640 using a diet-induced prediabetes murine model.
 
Methods: To determine whether CS0640 alters Th1, Th2, Th17 and Treg responses and the overall immune-endocrine responses in TBprediabetes murine model, the frequencies of these populations were assessed in lungs, blood, and mediastinal lymph nodes of male C57BL/6 mice collected at 3- and 8-weeks post-infection. Cytokine and immune-endocrine profiling were performed on serum, lung homogenates and lung cell suspensions. Correlation between the immune responses and lung histopathology scoring was assessed to determine M.tb infection severity.
 
Results: CS0640 regulates Th1, Th2 Th17, and Treg cell responses while altering inflammatory cytokine and hormone responses in lung, blood, and mediastinal lymph node compartments. The lung histopathology correlation also appears to be altered.
 
Conclusion: CS0640 alters immune-endocrine responses in TB-prediabetes thus impacting M.tb infection severity and may serve as a novel host-directed therapy for TB-T2D comorbidity treatments. 

Biography

Suzzana is a young research scientist with a keen interest in investigating the host immune response to Mycobacterium tuberculosis (M.tb) in TB-Type 2 diabetes comorbidity. Her research focuses on tuberculosis, diabetes, host-immune response to M.tb, and host-directed therapeutics.