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Type I Interferon Exacerbates Mycobacterium tuberculosis Induced Death of Human Macrophages

ABSTRACT: Type I interferons (IFN-I) are implicated in exacerbation of tuberculosis (TB), but the mechanisms are unclear. Mouse macrophages infected with Mycobacterium tuberculosis (Mtb) produce IFN-I, which contributes to their death. Here we investigate whether the same is true for human monocyte-derived macrophages (MDM). MDM prepared by a conventional method markedly upregulate interferon-stimulated genes (ISGs) upon Mtb infection, while MDM prepared to better restrict Mtb do so much less. A mixture of antibodies inhibiting IFN-I signaling prevents ISG induction. Surprisingly, secreted IFN-I are undetectable until nearly two days after ISG induction. These same antibodies do not diminish Mtb-infected MDM death. MDM induce ISGs in response to picogram/mL levels of exogenous IFN-I while depleting similar quantities from the medium. Exogenous IFN-I increase the proportion of dead MDM. We speculate that Mtb-infected MDM produce and respond to minute levels of IFN-I, and that only some of the resultant signaling is susceptible to neutralizing antibodies. Many types of cells may secrete IFN-I in patients with TB, where IFN-I is likely to promote the death of infected macrophages.

SUBMITTER: Dr. Angela Lee

PROVIDER: S-SCDT-10_1038-S44319-024-00171-0 | biostudies-other |

REPOSITORIES: biostudies-other

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Type I Interferon Exacerbates Mycobacterium tuberculosis Induced Human Macrophage Death

Project description:Type I Interferon Exacerbates Mycobacterium tuberculosis Induced Human Macrophage Death

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