Identification of a common immune signature in murine and human systemic Salmonellosis

Lee, Seung Joo; Liang, Li; Juárez, Silvia; Nanton, Minelva R.; Gondwe, Esther N.; Msefula, Chisomo; Kayala, Matthew A.; Necchi, Francesca; Heath, Jennifer N.; Hart, P. John; Tsolis, Renée M.; Heyderman, Robert S.; MacLennan, Calman A.; Felgner, Philip L.; Davies, D. Huw; McSorley, Stephen J.

doi:10.1073/pnas.1111413109

Cited by 86 publications

(99 citation statements)

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“…In previous studies, we described the production and use of a S. Typhi partial proteome microarray (∼63%) for profiling antibodies in human adult typhoid cases from Malawi, 9 Vietnam, 10 and Bangladesh, 18 and in the mouse S. Typhimurium model.…”

Section: Discussionmentioning

confidence: 99%

“…Full S. Typhi proteome microarrays (Antigen Discovery Inc., Irvine, CA) were manufactured according to published methods. 9,10 The content of the arrays comprised an ORFeome library cloned previously with ∼63% coverage of the S. Typhi proteome supplemented with the additional S. Typhi open reading frames (ORFs) to provide full coverage. In addition, LPSs from Salmonella typhosa (S. Typhi), purified by gel filtration (L2387; Sigma-Aldrich, Dorset, United Kingdom), 11 was printed in four 3-fold serial dilutions from 0.1 to 0.003 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

“…Serum samples were shipped to UCI on dry ice and were probed onto proteome arrays as described previously. 9,10 Arrays were scanned in a GenePix 4200AL (Molecular Devices, Sunnyvale, CA), and captured TIFF files were quantified using ScanArray Express software (Perkin Elmer, Waltham, MA). Median spot pixel intensities subtracted of local background were imported into Microsoft Excel (Microsoft Corp., Redmond, WA).…”

Section: Methodsmentioning

confidence: 99%

“…This is consistent with our previous studies. 9,10 Presumably, this is because of the high level of antigenic conservation of these antigens between S. Typhi and NTS serovars. Nevertheless, we did see some S. Typhi/ NTS discrimination using the array format, particularly by t1477-specific IgG, and LPS-specific IgA.…”

mentioning

confidence: 99%

“…10 In Bangladesh also, the same array revealed t1477 as the immunodominant antigen, able to discriminate between acute typhoid cases and uninfected controls in both serum and in plasmablast culture supernatants. 18 The t1477 antigen was not revealed as dominant in Malawian children, 9 although only two cases of typhoid were examined.…”

mentioning

confidence: 99%

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Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide

Davies

Jain

Nakajima

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger "hits," whereas the profile in U.S. adults was < 1/5 as broad, consistent with endemic exposure in Nigeria. Nigerian profiles were largely unaffected by clinical diagnosis, although the response against t1477 (hemolysin E) consistently emerged as stronger in typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide

Davies

Jain

Nakajima

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

et al. 2014

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CD4+ T cells and B cells are both essential for acquired immunity to Salmonella infection. It is well established that Salmonella inhibit host CD4+ T-cell responses, but a corresponding inhibitory effect on B cells is less well defined. Here, we utilize an antigen tetramer and pull-down enrichment strategy to directly visualize OVA-specific B cells in mice, as they respond to infection with Salmonella-OVA. Surprisingly, OVA-specific B-cell expansion and germinal center formation was not detected until bacteria were cleared from the host. Furthermore, Salmonella infection also actively inhibited both B- and T-cell responses to the same coinjected antigen but this did not require the presence of iNOS. The SPI2 locus has been shown to be responsible for inhibition of Salmonella-specific CD4+ T-cell responses, and an examination of SPI2-deficient bacteria demonstrated a recovery in B-cell expansion in infected mice. Together, these data suggest that Salmonella can simultaneously inhibit host B- and T-cell responses using SPI2-dependent mechanisms.

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Broadly reactive human CD4⁺ T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire

et al. 2020

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Enterobacteriaceae are a large family of Gram‐negative bacteria that includes both commensals and opportunistic pathogens. The latter can cause severe nosocomial infections, with outbreaks of multi‐antibiotics resistant strains, thus being a major public health threat. In this study, we report that Enterobacteriaceae‐reactive memory Th cells were highly enriched in a CCR6+CXCR3+ Th1*/17 cell subset and produced IFN‐γ, IL‐17A, and IL‐22. This T cell subset was severely reduced in septic patients with K. pneumoniae bloodstream infection who also selectively lacked circulating K. pneumonie‐reactive T cells. By combining heterologous antigenic stimulation, single cell cloning and TCR Vβ sequencing, we demonstrate that a large fraction of memory Th cell clones was broadly cross‐reactive to several Enterobacteriaceae species. These cross‐reactive Th cell clones were expanded in vivo and a large fraction of them recognized the conserved outer membrane protein A antigen. Interestingly, Enterobacteriaceae broadly cross‐reactive T cells were also prominent among in vitro primed naïve T cells. Collectively, these data point to the existence of immunodominant T cell epitopes shared among different Enterobacteriaceae species and targeted by cross‐reactive T cells that are readily found in the pre‐immune repertoire and are clonally expanded in the memory repertoire.

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Identification of a common immune signature in murine and human systemic Salmonellosis

Cited by 86 publications

References 65 publications

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide

Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

Broadly reactive human CD4⁺ T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire

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Identification of a common immune signature in murine and human systemic Salmonellosis

Cited by 86 publications

References 65 publications

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide

Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

Broadly reactive human CD4+ T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire

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Resources

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Broadly reactive human CD4⁺ T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire