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In vitro anti-mycobacterial effect of pH-responsive niosome loaded with lactoferricin via modulating inflammatory response-associated proteins in alveolar macrophage

ABSTRACT: Conventional antitubercular drugs for tuberculosis (TB) encounter a serious challenge related to the adverse outcomes caused by extended treatment duration and drug resistance. Thus, developing an innovative platform with effective anti-TB activity would offer more advantages.

ORGANISM(S): Cellular Organisms

SUBMITTER: Khajornsak Tragoolpua

PROVIDER: PXD061866 | JPOST Repository | Sun Mar 15 00:00:00 GMT 2026

REPOSITORIES: jPOST

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			Action	DRS
	Infected_Cell%20Empty_BC3_01_40782.mgf	Mgf
	Infected_Cell%20Empty_BC3_01_40782.mzXML	Mzxml
	Infected_Cell%20Empty_BC3_01_40783.mgf	Mgf
	Infected_Cell%20Empty_BC3_01_40783.mzXML	Mzxml
	Infected_Cell%20Empty_BC3_01_40784.mzXML	Mzxml

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Project description:Background: Tuberculosis (TB) remains a major public health problem, especially in developing countries, with 1.5 million deaths annually worldwide. Antibiotics are commonly used in the treatment of bacterial infections. As with most drugs, antibiotic treatment can also alter host metabolism, leading to adverse side-effects. Antibiotics can also interfere with the immune system, indirectly through the disturbance of the body’s microbiota or directly by modulating the functions of immune cells. It is therefore important to understand how antibiotic treatment modulates immune cell functions. Here we aim to evaluate the impact of first-line anti-TB drugs on the response of human macrophages infected with Mycobacterium tuberculosis (MTB). Results: Human macrophages were stimulated with heat-killed Mycobacterium tuberculosis (hk-MTB) and treated with isoniazid (INH), rifampicin (RIF), ethambutol, pyrazinamide (PZA) or amikacin (AMK). After 24h of treatment, RNA was collected and we characterized the genome-wide gene expression profiles of drug-treated cells by RNAseq. 556, 752 and 7 genes were differentially expressed in hk-MTB-stimulated macrophages upon RIF, PZA and EMB treatment respectively, whereas in uninfected macrophages, 448 and 11 genes were differentially expressed upon RIF and PZA treatment respectively. No genes were differentially expressed upon INH and AMK treatment. We classified all modulated genes by performing gene-set enrichment analysis. The gene set regulated by PZA in infected macrophages was significantly enriched for genes involved in Integral to lumenal side of endoplasmic reticulum membrane, Cytokine-mediated signaling pathway or Interferon-gamma-mediated signaling pathway. In hk-MTB-stimulated macrophages treated by RIF, we found an enrichment in Endoplasmic reticulum unfolded protein response, NADP binding or Lipid metabolic process. Conclusions: Our results highlight the importance to understand how antibiotic treatment modulates macrophage (Mφ) functions, and more generally, how it impacts the host immune response.

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In vitro anti-mycobacterial effect of pH-responsive niosome loaded with lactoferricin via modulating inflammatory response-associated proteins in alveolar macrophage

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