About: NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages

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About: NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages
Creator	Kim, Bae-Hoon Patten, Kelley Wang, Quiling Matta, Sumit David Sibley, L Macmicking, John Sk, Matta
Source	PMC
abstract	Phagocytic cells are the first line of innate defense against intracellular pathogens, and yet Toxoplasma gondii is renowned for its ability to survive in macrophages, although this paradigm is based on virulent type I parasites. Surprisingly, we find that avirulent type III parasites are preferentially cleared in naive macrophages, independent of gamma interferon (IFN-γ) activation. The ability of naive macrophages to clear type III parasites was dependent on enhanced activity of NADPH oxidase (Nox)-generated reactive oxygen species (ROS) and induction of guanylate binding protein 5 (Gbp5). Macrophages infected with type III parasites (CTG strain) showed a time-dependent increase in intracellular ROS generation that was higher than that induced by type I parasites (GT1 strain). The absence of Nox1 or Nox2, gp91 subunit isoforms of the Nox complex, reversed ROS-mediated clearance of CTG parasites. Consistent with this finding, both Nox1(−/−) and Nox2(−/−) mice showed higher susceptibility to CTG infection than wild-type mice. Additionally, Gbp5 expression was induced upon infection and the enhanced clearance of CTG strain parasites was reversed in Gbp5(−/−) macrophages. Expression of a type I ROP18 allele in CTG prevented clearance in naive macrophages, suggesting that it plays a role counteracting Gbp5. Although ROS and Gbp5 have been linked to activation of the NLRP3 inflammasome, clearance of CTG parasites did not rely on induction of pyroptosis. Collectively, these findings reveal that not all strains of T. gondii are adept at avoiding clearance in macrophages and define new roles for ROS and Gbps in controlling this important intracellular pathogen.
has issue date	2018-08-28(xsd:dateTime)
bibo:doi	10.1128/mbio.01393-18
bibo:pmid	30154263
has license	cc-by
sha1sum (hex)	e6072267b50da2dfa7595ddd3e29fe99a96d4624
schema:url	https://doi.org/10.1128/mbio.01393-18
resource representing a document's title	NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages
has PubMed Central identifier	PMC6113620
has PubMed identifier	30154263
schema:publication	mBio
resource representing a document's body	covid:e6072267b50da2dfa7595ddd3e29fe99a96d4624#body_text
is schema:about of	named entity 'RESTRICT' named entity 'enhanced' named entity 'strains' named entity 'complex' named entity 'induction' named entity 'caused' named entity 'Nox2' named entity 'NLRP3' named entity 'control' named entity 'mice' named entity 'clear' named entity 'induction' named entity 'macrophages' named entity 'limiting' named entity 'dependent' named entity 'Gbps' named entity 'Macrophages' named entity 'macrophages' named entity 'Nox' named entity 'Binding' named entity 'SURVIVAL' named entity 'TOXOPLASMA GONDII' named entity 'EXTEND' named entity 'ISOFORMS' named entity 'GAMMA INTERFERON' named entity 'INTRINSIC' named entity 'DEFENSE MECHANISMS' named entity 'NOX2' named entity 'REACTIVE OXYGEN SPECIES' named entity 'TYPE III' named entity 'HOST' named entity 'PARASITES' named entity 'TO CONTROL' named entity 'USING' named entity 'FUNCTIONS' named entity 'PRESENT' named entity 'CELLS' named entity 'DEPENDENT' named entity 'WITH TYPE' named entity 'NOVEL' named entity 'EXPRESSION' named entity 'IN VITRO' named entity 'LIMITING' named entity 'RESPONSES' named entity 'COMPLETELY UNDERSTAND' named entity 'REVEAL' named entity 'INFECTED' named entity 'DID' named entity 'LEVEL' named entity 'TOXOPLASMA INFECTIONS' named entity 'HIGHER' named entity 'INDUCTION' named entity 'CLEARED' named entity 'PARASITIC' named entity 'ABSENCE OF' named entity 'ROLE' named entity 'TOXOPLASMOSIS' named entity 'ACTIVATION' named entity 'NOX' named entity 'APICOMPLEXAN' named entity 'INFECTIONS' named entity 'MACROPHAGES' named entity 'PYROPTOSIS' named entity 'STRAINS' named entity 'TOXOPLASMA' named entity 'INCREASE' named entity 'INDEPENDENT OF' named entity 'REVERSED' named entity 'DEFENSE' named entity 'ITS' named entity 'CONTROLLED BY' named entity 'INDUCED' named entity 'HUMANS' named entity 'INFECTION' named entity 'PARADIGM'

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