Host gene expression for Mycobacterium avium subsp. paratuberculosis infection in human THP-1 macrophages

Area of Science:

• Immunology
• Microbiology
• Genomics

Background:

• Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease in cattle, leading to economic losses.
• MAP's potential link to human Crohn's disease (CD) and its presence in pasteurized milk raise public health concerns.
• Limited research exists on MAP interactions with human cells, particularly regarding host immune responses.

Purpose of the Study:

• To investigate the host-pathogen interactions between MAP and human cells at the transcriptional level.
• To identify specific host immune response genes and metabolic pathways affected by MAP infection.
• To validate findings from a murine model and cattle in human monocyte-derived macrophage (THP-1) cells.

Main Methods:

• Ingenuity Pathway Analysis (IPA) was applied to transcription profiles from a murine MAP infection model.
• Gene expression data were compared between MAP-infected mice, naturally MAP-infected cattle, and MAP-infected human THP-1 cells.
• Validation of selected host immune response genes in MAP-infected human THP-1 cells.

Main Results:

• Twenty-one genes were identified as potential host immune responses to MAP infection.
• Significant up-regulation of immune response genes (e.g., CD14, S100A8, S100A9) and Th1-polarizing factors (e.g., CCL4, CXCL9) was observed.
• Down-regulation of certain metabolism-related genes (e.g., IGF1, MPO) and no significant change in others (e.g., IFNG) were noted in THP-1 cells.

Conclusions:

• MAP infection triggers specific immune responses and metabolic alterations in human macrophages.
• The study provides insights into host-pathogen interactions relevant to MAP's potential role in human diseases like CD.
• Further research is warranted to elucidate the precise mechanisms of MAP pathogenesis in humans.