NTR: 'symbiont-mediated suppression of host pro-inflammatory cytokine production' and symbiont-mediated suppression of host anti-inflammatory cytokine production'

[pgaudet]

For GO-PathGO alignment

Children of symbiont-mediated suppression of host cytokine production'

[pgaudet]

From @genegodbold

Anti-inflammatory cytokines include: interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-11, and IL-13 Pro-inflammatory cytokines include: IL-1, IL-12, IL-18, TNF, IFN-gamma, GM-CSF

[pgaudet]

+[Term] +id: GO:0141173 +name: symbiont-mediated suppression of host pro-inflammatory cytokine ~production~ signaling +namespace: biological_process +def: "A process by which a symbiont inhibits or disrupts pro-inflammatory cytokine production in the host organism. Pro-inflammatory cytokines include: IL-1, IL-12, IL-18, TNF, IFN-gamma, and GM-CSF. The host is defined as the larger of the organisms involved in a symbiotic interaction." [GOC:pg] +synonym: "negative regulation by symbiont of host pro-inflammatory cytokine production" EXACT [] +synonym: "suppression by symbiont of host pro-inflammatory cytokine production" EXACT [] +synonym: "suppression by symbiont of host pro-inflammatory cytokine secretion" RELATED [] +is_a: GO:0140133 ! symbiont-mediated suppression of host cytokine production +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/27129" xsd:anyURI +created_by: pg +creation_date: 2024-02-22T16:33:40Z + +[Term] +id: GO:0141174 +name: symbiont-mediated suppression of host anti-inflammatory cytokine ~production~ signaling +namespace: biological_process +def: "A process by which a symbiont inhibits or disrupts anti-inflammatory cytokine production in the host organism. Anti-inflammatory cytokines include: interleukin (IL)-1, IL-4, IL-6, IL-10, IL-11, and IL-13. The host is defined as the larger of the organisms involved in a symbiotic interaction." [GOC:pg] +synonym: "negative regulation by symbiont of host anti-inflammatory cytokine production" EXACT [] +synonym: "suppression by symbiont of host anti-inflammatory cytokine production" EXACT [] +synonym: "suppression by symbiont of host anti-inflammatory cytokine secretion" RELATED [] +is_a: GO:0140133 ! symbiont-mediated suppression of host cytokine production +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/27129" xsd:anyURI +created_by: pg +creation_date: 2024-02-22T16:35:54Z

[pgaudet]

@genegodbold please provide references.

[genegodbold]

@pgaudet, I don't think I have any sequences that suppress anti-inflammatory cytokine production. Instead I have those that suppress pro-inflammatory cytokine production and that activate anti-inflammatory cytokine production. Could we make a new GO term "symbiont-mediated activation of host anti-inflammatory cytokine production". In bacteria, this latter phenomenon seems pretty widespread.

Bacterial symbiont-mediated activation of host anti-inflammatory cytokine signaling ~production~:

• PE15 (Rv1386) from Mycobacterium tuberculosis: PE5 and PE15 are 75% similar and are highly conserved in M_tuberculosis complex. When PE15 is expressed in the nonpathogenic M. smegmatis and used to infect cultured macrophages, the bacteria down-regulate expression of host iNOS and trigger activation of the host MAP kinases leading to production of the anti-inflammatory cytokine interleukin-10 [PMID23284742].
• Salmonella anti-inflammatory response activator (SarA): Salmonella Typhimurium effector SarA associates with and activates host STAT3 in a murine lymphoblastoid cell line. It is both necessary and sufficient for STAT3 phosphorylation thereby activating host anti-inflammatory cytokine IL-10 production. Deletion eliminates IL-10 induction while introduction of a SarA encoding plasmid restores it. SarA activity promotes intracellular replication. It can be secreted by SPI-1 and SPI-2. SarA activation of STAT3 both promotes growth and immune evasion [PMID:27437422][PMID:29924996].
• YopM is an immunosuppressive effector of Yersinia enterocolitica that exits the nucleus of host cells via the host DEAD-box helicase 3 (DDX3) and the host CRM1 nuclear export pathway. Increased YopM levels in the nucleus enhances phosphorylation of host ribosomal S6 kinase 1 (RSK1). Interaction of RSK1 with YopM increases the host anti-inflammatory IL-10 mRNA [PMID:27300509].

These bacterial proteins suppress pro-inflammatory cytokine production AND activate anti-inflammatory cytokine production.

• Bordetella outer protein N (BopN) is an effector secreted via the T3SS of Bordetella. Its N terminus mediates translocation into the host cell nucleus while the C terminal portion blocks host NFkappaB p65 translocation into the nucleus. BopN induces production of host anti-inflammatory cytokine interleukin-10. A bacterial strain in which the gene encoding BopN was deleted was unable to induce interleukin-10 production in mice, resulting in the elimination of bacteria by neutrophil infiltration into the lung alveoli. The up-regulation of IL-10 by the BopN effector, resulting in the suppression of IFN-gamma signaling, is a significant stealth strategy by which Bordetella evades the host immune system [PMID:20008527]. BopN blocks nuclear translocation of subunit p50 to induce IL-10 expression [PMID:21383764].
• Proline racemase protein A (PrpA) from Brucellae: PrpA is responsible for chronic infection by brucellae in mice. PrpA induces a transient anergic state of the host immune system and promotes the establishment of a chronic infection. PrpA acts as a B cell mitogen and alters B cell cytokine production. PrpA downregulates host interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) while upregulating transforming growth factor beta1 (TGFbeta1) and interleukin-10 altering the immune response from pro-inflammatory to anti-inflammatory [PMID:24508400].
• Antigen 84 (MAP1889c, Wag31) from Myclolicibacerium paratuberculosis (formerly Mycobacterium avium): MAP1889c activates the maturation of host dendritic cells, through TLR4 activation of host MAPK (ERK1/2 and p38) and NFkappaB, to secrete the anti-inflammatory cytokine interleukin-10 (IL-10); this also involved phosphorylation of host CREB. MAP1889c activated dendritic cells secrete lower amounts of pro-inflammatory cytokines IL-6, IL-12, and TNF. Dendritic cells matured through MAP1889c activity induced proliferation of T cells and drove a Th2 immune response. It promotes intracellular bacterial survival [PMID:32290379].
• PE31 from Mycobacterium tuberculosis: THP-1 macrophages infected with M. smegmatis expressing the M. tuberculosis protein PE31 exhibit down-regulation of pro-inflammatory cytokines IL-12 p40 and IL-6 as well as increased production of anti-inflammatory cytokine IL-10. The infected macrophages also upregulate expression of the host interferon-stimulated GTPase guanylate-binding protein-1 (GBP-1) when compared to macrophage infected with bacteria only expressing control vector. This occurs through regulation of the NFkappaB pathway [PMID:32117813].

[pgaudet]

@genegodbold to provide reference for the proteins that inhibit cytokine signaling (done during GO-PathGO alignment call)

[pgaudet]

+[Term] +id: GO:0141184 +name: symbiont-mediated activation of host anti-inflammatory cytokine signaling +namespace: biological_process +def: "A process in which a symbiont subverts an anti-inflammatory cytokine signaling pathway in the host organism by initiating, promoting, or enhancing its activation." [PMID:23284742, PMID:27437422, PMID:29924996] +is_a: GO:0052028 ! symbiont-mediated activation of host signal transduction pathway +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/27129" xsd:anyURI +created_by: pg +creation_date: 2024-03-19T13:30:47Z