Proteomics

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Cysteine reactivity profiling identifies host regulators of Mycobacterium tuberculosis replication in human macrophages

ABSTRACT: Innate immune cells such as monocytes and macrophages provide the earliest defense against infection by intracellular pathogens by initiating signaling pathways and restricting pathogen replication. However, the full complement of proteins that mediate cell-autonomous immunity remains incompletely defined. Here, we applied cysteine-directed activity-based protein profiling (ABPP) to map proteome-wide cysteine reactivity changes in THP-1 monocytes and primary human monocyte-derived macrophages during Mycobacterium tuberculosis (Mtb) infection. Across both cell types, we quantified 148 cysteine residues with altered reactivity. Genetic perturbation of a subset of proteins harboring these changes significantly impacted Mtb replication, revealing functional links between site-specific cysteine reactivity and antimicrobial defense. These data define previously unrecognized host protein changes during Mtb infection and provide a resource for investigating post-translational events that regulate innate immune responses to intracellular bacteria.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Kristen DeMeester  

LAB HEAD: Benjamin Cravatt

PROVIDER: PXD067709 | Pride | 2026-03-02

REPOSITORIES: Pride

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Dataset's files

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20200706_THP1_MTB_KB05_4h_1to10_Rep1_01.raw Raw
20200706_THP1_MTB_KB05_4h_1to10_Rep1_02.raw Raw
20200706_THP1_MTB_KB05_4h_1to10_Rep1_03.raw Raw
20200706_THP1_MTB_KB05_4h_1to10_Rep1_04.raw Raw
20200706_THP1_MTB_KB05_4h_1to10_Rep1_05.raw Raw
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Publications

Cysteine Reactivity Profiling Identifies Host Regulators of <i>Mycobacterium tuberculosis</i> Replication in Human Macrophages.

Neff John K JK   DeMeester Kristen E KE   Párraga Solórzano Paola K PK   Suciu Radu M RM   Dix Melissa M MM   Simon Gabriel G   Gianakopoulos Max A MA   Melillo Bruno B   Cravatt Benjamin F BF   Shiloh Michael U MU  

ACS infectious diseases 20260127 2

Innate immune cells, such as monocytes and macrophages, provide the earliest defense against intracellular pathogen infection by initiating signaling pathways and restricting pathogen replication. However, the full complement of proteins that mediate cell-autonomous immunity remains incompletely defined. Here, we applied cysteine-directed activity-based protein profiling (ABPP) to map proteome-wide cysteine reactivity changes in THP-1 monocytes and primary human monocyte-derived macrophages duri  ...[more]

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