Stephen J Mcsorley (Reviewer) Center for Comparative Medicine University of California Davis

. 2018 October 9;115(41):10416-10421.

doi: 10.1073/pnas.1808339115. Epub 2018 Sep 25.

Optimal protection against Salmonella infection requires noncirculating memory

Newton G Peres ³ , Nancy Wang ³ , Oanh H Pham ^{1 two} , Victoria L Rudisill ^{1 2} , Zachary N Fogassy ^{i ii} , Paul G Whitney ^three , Daniel Fernandez-Ruiz ³ , Thomas Gebhardt ³ , Quynh-Mai Pham ⁴ , Lynn Puddington ⁴ , Sammy Bedoui ⁱⁱⁱ , Richard A Strugnell ³ , Stephen J McSorley ^{v 2}

Affiliations

• PMID: 30254173
• PMCID: PMC6187142
• DOI: 10.1073/pnas.1808339115

Free PMC article

Optimal protection against Salmonella infection requires noncirculating memory

Joseph M Benoun  et al. Proc Natl Acad Sci U Due south A. 2018 .

Free PMC article

Abstract

While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we plant that constructive protection correlated with expanded Salmonella-specific retentivity CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP-IFN-γ reporter organisation, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver retention cells afterwards ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these information demonstrate that noncirculating retentiveness Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.

Keywords: CD4 T cell; Salmonella infection; protective immunity; tissue-resident retention; vaccines.

Conflict of involvement argument

The authors declare no conflict of interest.

Figures

Fig. i.

Immunization with LVS Salmonella confers long-lasting protection confronting Salmonella infection. (A and B) Mice were immunized with 2.5 × 10⁶ cfu/mouse intravenously (BRD509-2W1S). Mice were challenged orally 45 d afterwards with 1 × ten⁹ cfu/mL SL1344 via water bottle exposure. Mice were euthanized on mean solar day 5 post challenge, and bacterial burdens were analyzed in spleen and liver. Data show hateful ± SEM of two replicative experiments with three to six mice per group. (C and D) Mice were immunized with 5 × 10⁵ cfu/mouse intravenously (BRD509-2W1S), and on indicated days subsequently mice were challenged with 1 × 10^ix cfu/mL SL1344 via h2o canteen exposure. Mice were euthanized on twenty-four hour period 5 post challenge, and bacterial burdens were analyzed in the spleen and liver. Data show mean ± SEM with 4 to 8 mice per grouping per time indicate. ****P < 0.0001.

Fig. 2.

Circulating and resident Salmonella-specific CD4 memory T cells are generated afterward LVS immunization. (A) Generation of circulating tetramer+ CD4 T cells by LVS immunization. Blood and spleen samples were collected from naive and LVS immunized mice (2.five × 10⁶ cfu/mouse intravenous BRD509-2W1S) 42 d afterward immunization. Lymphocytes were isolated, stained, and tetramer-positive cell events were quantified. Data show mean ± SEM of at least four mice per group. **P < 0.01. (B) Representative period plot and quantitation of IFN-γ⁺T-bet^high CD4 T cells from mice immunized equally in A. Data bear witness hateful ± SEM of pooled data from two replicative experiments. ****P < 0.0001. (C and D) Representative menstruation plots and pooled analysis from LVS-immunized mice (2.five × 10^{half dozen} cfu/mouse i.five.). On day 45 afterwards immunization, mice were administered anti-CD45.2 antibiotic (iii µg/mouse) iii min before euthanasia. Organs were harvested and digested before lymphocytes were stained and quantified. Data show mean ± SEM with vi mice per grouping.

Fig. 3.

LVS immunization induces noncirculating Salmonella-specific memory CD4 T cells. Congenically marked CD45.ii mice previously immunized intravenously with two.5 × 10^vi cfu/mouse were surgically joined to CD45.1 mice for 28 d. Mice were separated, and tissues were harvested 14 d afterwards. (A) Tetramer numbers in spleens from naive, naive parabiont, and LVS-immunized parabionts. Splenocytes were compared with naive and LVS-immunized parabionts for presence of the CD45.two congenic marker. (B) Tetramer numbers in spleen (Left) and liver (Right) from naive and LVS-immunized parabionts. Tissue lymphocytes were compared between naive and LVS-immunized parabionts for presence of the CD45.ii congenic marking. Data show mean ± SEM from three mice per group. *P < 0.05.

Fig. 4.

Both tissue-resident and circulating retention are required for optimal protective immunity against Salmonella infection. (A) Congenically marked CD45.2 mice were immunized and boosted with ii.five × 10⁶ cfu/mouse, and threescore d later were surgically joined to CD45.1 mice for 30 d. Mice were separated and challenged intravenously 14 d later with i × 10³ cfu/mouse SL1344. Mice were then euthanized 6 d mail challenge. Spleens (B) and livers (C) were harvested, homogenized, diluted, and plated to determine bacterial burden in each tissue. Data show the mean of two replicative experiments ±SEM with five to 7 mice per grouping. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Fig. 5.

CD69^Hi Th1 cells in the liver display markers of tissue residence. (A–H) IFN-γ-eYFP mice were immunized intravenously with 200 cfu of TAS2010, and 12 wk later spleens and livers were assessed by menses cytometry. (A and B) Representative plots and pooled percentages of CD69+ eYFP+ CD4+ T cells from immunized mice. (C–H) FACS plots comparing the expression of P2X7, ARTC2, CD101, LFA-1, CD103, and KLRG1 by eYFP+ CD69^{how-do-you-do} (solid black line) and eYFP+ CD69^lo (gray shading) CD4+ T cells in the liver 12 wk afterward TAS2010 immunization. Data are representative of pools of (A–H) two independent experiments. (B) n = 8. (C–H) n = half dozen per group. **P < 0.01, ****P < 0.0001.

Fig. 6.

Liver-associated IFN-γ⁺ CD4⁺ T cells protect confronting SL1344 infection. (A–C) Survival of Rag2 ^−/− × Il2rg ^−/− mice receiving five × 10^seven splenocytes or 1 × ten⁷ lymphocyte-enriched liver cells from C57BL/vi mice that were previously infected for 12 wk and received l µg S+16a or PBS past intravenous injection 15 min before harvest. (A) Recipients were challenged intravenously with 200 cfu SL1344 24 h after adoptive transfer. (B) At the time of cell transfer, recipients of S+16a-treated liver cells received intraperitoneal injections of 250 µg of isotype control or anti-CD4 (GK1.5) or 200 µg anti–IFN-γ (HB-170-15), and 20 h subsequently, recipients were challenged intravenously with 200 cfu SL1344. Antibiotic treatments were repeated intraperitoneally every three–4 d. (C) Distribution of CD69⁺ eYFP⁺ CD4⁺ T cells in Rag2 ^−/− × Il2rg ^−/− mice that had been adoptively transferred with liver cells from C57BL/half dozen mice infected for 12 wk that received fifty µg South+16a or PBS. Data in A and B are representative of three independent experiments. Data in C are representative of ii independent experiments. (B) n = vii–eight. (C) north = 7–12 per group.

Similar articles

• Soluble flagellin, FliC, induces an Ag-specific Th2 response, notwithstanding promotes T-bet-regulated Th1 clearance of Salmonella typhimurium infection.

  Bobat S, Flores-Langarica A, Hitchcock J, Marshall JL, Kingsley RA, Goodall Thousand, Gil-Cruz C, Serre K, Leyton DL, Letran SE, Gaspal F, Chester R, Chamberlain JL, Dougan G, López-Macías C, Henderson IR, Alexander J, MacLennan IC, Cunningham AF. Bobat S, et al. Eur J Immunol. 2011 Jun;41(half-dozen):1606-18. doi: 10.1002/eji.201041089. Epub 2011 May 10. Eur J Immunol. 2011. PMID: 21469112

• IκBζ facilitates protective immunity against Salmonella infection via Th1 differentiation and IgG production.

  Ahn JH, Cho J, Kwon BE, Lee GS, Yoon SI, Kang SG, Kim PH, Kweon MN, Yang H, Vallance BA, Kim YI, Chang SY, Ko HJ. Ahn JH, et al. Sci Rep. 2019 Jun 10;ix(ane):8397. doi: 10.1038/s41598-019-44019-3. Sci Rep. 2019. PMID: 31182790 Costless PMC commodity.

• Differential effect of infection with attenuated Salmonella in MyD88-scarce mice is dependent on the route of administration.

  Issac JM, Sarawathiamma D, Al-Ketbi MI, Azimullah S, Al-Ojali SM, Mohamed YA, Flavell RA, Fernandez-Cabezudo MJ, al-Ramadi BK. Issac JM, et al. Immunobiology. 2013 Jan;218(i):52-63. doi: 10.1016/j.imbio.2012.02.001. Epub 2012 Feb x. Immunobiology. 2013. PMID: 22386951

• Salmonella type III-mediated heterologous antigen delivery: a versatile oral vaccination strategy to induce cellular amnesty confronting infectious agents and tumors.

  Panthel 1000, Meinel KM, Sevil Domènech VE, Trülzsch One thousand, Rüssmann H. Panthel G, et al. Int J Med Microbiol. 2008 Jan;298(1-2):99-103. doi: 10.1016/j.ijmm.2007.07.002. Epub 2007 Aug 23. Int J Med Microbiol. 2008. PMID: 17719275 Review.

• Collateral Impairment: Detrimental Effect of Antibiotics on the Development of Protective Immune Memory.

  Benoun JM, Labuda JC, McSorley SJ. Benoun JM, et al. mBio. 2016 December 20;7(six):e01520-16. doi: 10.1128/mBio.01520-16. mBio. 2016. PMID: 27999159 Free PMC article. Review.

Cited by twenty articles

• CD4+ T jail cell immunity to Salmonella is transient in the circulation.

  Peres NG, Wang N, Whitney P, Engel S, Shreenivas MM, Comerford I, Hocking DM, Erazo AB, Förster I, Kupz A, Gebhardt T, McColl SR, McSorley SJ, Bedoui S, Strugnell RA. Peres NG, et al. PLoS Pathog. 2021 Oct 25;17(ten):e1010004. doi: 10.1371/journal.ppat.1010004. eCollection 2021 Oct. PLoS Pathog. 2021. PMID: 34695149 Gratuitous PMC commodity.

• Tissue-Resident Memory T Cells in Antifungal Immunity.

  LeibundGut-Landmann S. LeibundGut-Landmann S. Front Immunol. 2021 May 25;12:693055. doi: ten.3389/fimmu.2021.693055. eCollection 2021. Front Immunol. 2021. PMID: 34113356 Gratis PMC article. Review.

• Regulation of Th1 T Cell Differentiation by Iron via Upregulation of T Cell Immunoglobulin and Mucin Containing Poly peptide-3 (TIM-3).

  Pfeifhofer-Obermair C, Tymoszuk P, Nairz G, Schroll A, Klais 1000, Demetz Eastward, Engl S, Brigo N, Weiss G. Pfeifhofer-Obermair C, et al. Front Immunol. 2021 May 24;12:637809. doi: 10.3389/fimmu.2021.637809. eCollection 2021. Forepart Immunol. 2021. PMID: 34108960 Free PMC article.

• Circulating immunity protects the female reproductive tract from Chlamydia infection.

  Labuda JC, Pham OH, Depew CE, Fong KD, Lee BS, Rixon JA, McSorley SJ. Labuda JC, et al. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2104407118. doi: 10.1073/pnas.2104407118. Proc Natl Acad Sci U S A. 2021. PMID: 34001624 Free PMC commodity.

• CD4+ and CD8+ Circulating Memory T Cells Are Crucial in the Protection Induced by Vaccination with Salmonella Typhi Porins.

  Ontiveros-Padilla Fifty, García-Lozano A, Tepale-Segura A, Rivera-Hernández T, Pastelin-Palacios R, Isibasi A, Arriaga-Pizano LA, Bonifaz LC, López-Macías C. Ontiveros-Padilla L, et al. Microorganisms. 2021 Apr vii;9(four):770. doi: 10.3390/microorganisms9040770. Microorganisms. 2021. PMID: 33916894 Free PMC article.

Publication types

MeSH terms

LinkOut - more resource

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • scite Smart Citations

• Medical

  • MedlinePlus Health Information

• Molecular Biological science Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Label Plan

kingropened.blogspot.com

Source: https://pubmed.ncbi.nlm.nih.gov/30254173/

Share this post