General Information of HIF (ID: HIFC0068)
HIF Name	CD4+ helper T cells
HIF Synonym(s)	CD4+ TH1 cells, CD4+ helper T cells
HIF Classification	T cells (TCs)
Description	T helper type 1 (Th1) cells are a lineage of CD4 + effector T cellthat promotes cell-mediated immune responses and is required for host defense against intracellular viral and bacterial pathogens.				[1]

Microbe Species (MIC) Regulated by This HIF
Barnesiella intestinihominis (CFB bacteria)			MIC00192
Description	The colon resident Gram Barnesiella intestinihominis boosted systemic polyfunctional Th1 cell responses.				[2]
Bifidobacterium animalis subsp. lactis (actinobacteria)			MIC00216
Description	Bifidobacterium animalis subsp. lactis has the intrinsic ability to promote a Th1 immune response through an increase in IL-12/IL-23.				[3]
Bilophila wadsworthia (delta-proteobacteria)			MIC00235
Description	Bilophila is associated with T-helper type 1 cells responses.				[4]
Blautia obeum (firmicutes)			MIC00240
Description	Blautia obeum is associated with T-helper type 1 cells responses.				[5]
Bordetella pertussis (beta-proteobacteria)			MIC00248
Description	Th1 response was promoted after parenteral immunization of mice with an experimental acellular pertussis vaccine formulated with LP-GMP, which conferred protection against lung infection with Bordetella pertussis.				[6]
Brucella ovis (alpha-proteobacteria)			MIC00273
Description	A less intense Th1 pattern was found from naive splenic cells stimulated by Brucella ovis.				[7]
Clostridium butyricum (firmicutes)			MIC00388
Description	Clostridium butyricum CGMCC0313.1 reduces pancreas inflammation and reversed the imbalance in Th1/Th2/Th17/Tregs.				[8]
Clostridium leptum (firmicutes)			MIC00402
Description	Early-life Clostridium leptum exposure induced an immunosuppressive environment in the lung, resulting in the inhibition of Th1 cell responses.				[9]
Dialister pneumosintes (firmicutes)			MIC00506
Description	An increased levels of Dialister was accompanied by altered Th1/Th2 ratios.				[10]
Ehrlichia chaffeensis (alpha-proteobacteria)			MIC00523
Description	Ehrlichia chaffeensis lipoproteins could induce DTH reactions which were elicited by CD4+ and CD8+ T cells of the Th1 subset.				[11]
Enterococcus durans (firmicutes)			MIC00547
Description	Enterococcus durans presented a profile toward a mild inflammatory Th1 response.				[12]
Haemophilus ducreyi (gamma-proteobacteria)			MIC00650
Description	Haemophilus ducreyi induced Th1 cells to secrete interleukin-2.				[13]
Helicobacter acinonychis (epsilon-proteobacteria)			MIC00662
Description	Helicobacter acinonychis is associated with T-helper type 1 cells responses.				[14]
Helicobacter cinaedi (epsilon-proteobacteria)			MIC00665
Description	IgG2 serological markers for Th1 responses were significantly increased in subjects infected with WT Helicobacter cinaedi compared with uninfected controls.				[15]
Hungatella hathewayi (firmicutes)			MIC00397
Description	Hungatella hathewayi is a low secretor of IL-10 on the Th1-driven inflammatory response to DNBS.				[16]
Lactobacillus reuteri (firmicutes)			MIC00731
Description	Lactobacillus reuteri could mediate suppression of T-helper type 1(Th1) cells responses.				[17]
Lactococcus lactis (firmicutes)			MIC00745
Description	Certain Lactococcus lactis strains isolated from the environment were proved capable of promoting Th1 bias immune response.				[18]
Leptospira borgpetersenii (spirochaetes)			MIC00758
Description	Th1 cells developed an adaptive immune response by production of IgG2 antigen-specific antibodies following Leptospira borgpetersenii infection.				[19]
Leuconostoc mesenteroides (firmicutes)			MIC00766
Description	Leuconostoc mesenteroides can induce of Th1 cytokines under Th2-type conditions.				[20]
Methanobrevibacter smithii (euryarchaeotes)			MIC00792
Description	Methanobrevibacter smithii archaeosomes-entrapped mzNL4-3 VLPs specifically induced and augmented T-helper type 1 cells oriented responses against HIV antigens.				[21]
Mycobacterium ulcerans (actinobacteria)			MIC00852
Description	Mycobacterium marinum induced significant T-helper type 1 cells immunity.				[22]
Mycobacterium parascrofulaceum (actinobacteria)			MIC00853
Description	Th1 and Th17 responses crossregulate each other during Mycobacterium parascrofulaceum infection.				[23]
Neisseria meningitidis (beta-proteobacteria)			MIC00891
Description	Neisseria meningitidis induced more TH1 cytokine (low IL-10/IFN- ratio) in young children.				[24]
Pantoea agglomerans (enterobacteria)			MIC00944
Description	Lipopolysaccharides derived from Pantoea agglomerans stimulated macrophages which normalized the T-helper type 1 and 2 (Th1/Th2) immune system balance.				[25]
Pasteurella dagmatis (gamma-proteobacteria)			MIC00966
Description	Pasteurellaceae was associated with Th1-type immune response.				[26]
Prevotella copri (CFB bacteria)			MIC01010
Description	A 27-kD protein of Prevotella copri stimulated Th1 responses in some new-onset rheumatoid arthritis patients.				[27]
Pseudomonas aeruginosa (gamma-proteobacteria)			MIC01054
Description	A kill or inactivate but metabolically active Pseudomonas aeruginosa(deactivate enzymatic activity)could elicit Th1 pathways of cell-mediated immune responses.				[28]
Rickettsia prowazekii (alpha-proteobacteria)			MIC01108
Description	Th1 response was associated with IgG2a/IgG2b isotype secretion during Rickettsia prowazekii infection.				[29]
Rickettsia rickettsii (alpha-proteobacteria)			MIC01109
Description	Th1 epitope peptides can induce protective immunity against Rickettsia rickettsii infection.				[30]
Salmonella enterica subsp. enterica (enterobacteria)			MIC01154
Description	Salmonella typhimurium could increase Th1 responses.				[31]
Stenotrophomonas maltophilia (gamma-proteobacteria)			MIC01231
Description	Intranasal immunization with Stenotrophomonas maltophilia recombinant OmpA may trigger Th1-mediated cellular immune responses.				[32]
Streptobacillus moniliformis (fusobacteria)			MIC01235
Description	Streptobacillus moniliformis is associated with T-helper type 1 cellsTh1) responses.				[33]
Trichophyton tonsurans (ascomycetes)			MIC01333
Description	Trichophyton tonsurans can produce Th1 cell cytokine profiles.				[34]
Yersinia pestis (enterobacteria)			MIC01401
Description	Yersinia could paticipate in Th1 responses.				[35]

References
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2	Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects. Immunity. 2016 Oct 18;45(4):931-943. doi: 10.1016/j.immuni.2016.09.009. Epub 2016 Oct 4.
3	Investigation of the immunomodulatory effects of Lactobacillus casei and Bifidobacterium lactis on Helicobacter pylori infection. Helicobacter. 2008 Jun;13(3):183-90. doi: 10.1111/j.1523-5378.2008.00595.x.
4	Interactions between Diet, Bile Acid Metabolism, Gut Microbiota, and Inflammatory Bowel Diseases. Dig Dis. 2015;33(3):351-6. doi: 10.1159/000371687. Epub 2015 May 27.
5	Circulating and Tissue-Resident CD4(+) T Cells With Reactivity to Intestinal Microbiota Are Abundant in Healthy Individuals and Function Is Altered During Inflammation. Gastroenterology. 2017 Nov;153(5):1320-1337.e16. doi: 10.1053/j.gastro.2017.07.047. Epub 2017 Aug 4.
6	Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting T(RM) cells. Mucosal Immunol. 2018 Nov;11(6):1763-1776. doi: 10.1038/s41385-018-0080-x. Epub 2018 Aug 20.
7	Modulation of the cellular immune response after oral or subcutaneous immunization with microparticles containing Brucella ovis antigens. J Control Release. 2002 Dec 13;85(1-3):237-46. doi: 10.1016/s0168-3659(02)00276-6.
8	Clostridium butyricum CGMCC0313.1 Protects against Autoimmune Diabetes by Modulating Intestinal Immune Homeostasis and Inducing Pancreatic Regulatory T Cells. Front Immunol. 2017 Oct 19;8:1345. doi: 10.3389/fimmu.2017.01345. eCollection 2017.
9	Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression. PLoS One. 2015 Nov 13;10(11):e0141717. doi: 10.1371/journal.pone.0141717. eCollection 2015.
10	Host-bacterial interactions during induction and resolution of experimental gingivitis in current smokers. J Periodontol. 2013 Jan;84(1):32-40. doi: 10.1902/jop.2012.110662. Epub 2012 Mar 16.
11	Proteomic analysis of and immune responses to Ehrlichia chaffeensis lipoproteins. Infect Immun. 2008 Aug;76(8):3405-14. doi: 10.1128/IAI.00056-08. Epub 2008 May 19.
12	Enterococcus durans EP1 a Promising Anti-inflammatory Probiotic Able to Stimulate sIgA and to Increase Faecalibacterium prausnitzii Abundance. Front Immunol. 2017 Feb 10;8:88. doi: 10.3389/fimmu.2017.00088. eCollection 2017.
13	The immune response to Haemophilus ducreyi resembles a delayed-type hypersensitivity reaction throughout experimental infection of human subjects. J Infect Dis. 1998 Dec;178(6):1688-97. doi: 10.1086/314489.
14	Recombinant Bacillus subtilis Spores Elicit Th1/Th17-Polarized Immune Response in a Murine Model of Helicobacter pylori Vaccination. Mol Biotechnol. 2015 Aug;57(8):685-91. doi: 10.1007/s12033-015-9859-0.
15	Alkyl hydroperoxide reductase is required for Helicobacter cinaedi intestinal colonization and survival under oxidative stress in BALB/c and BALB/c interleukin-10-/- mice. Infect Immun. 2012 Mar;80(3):921-8. doi: 10.1128/IAI.05477-11. Epub 2011 Dec 19.
16	Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses. Sci Rep. 2016 Jan 4;6:18507. doi: 10.1038/srep18507.
17	Probiotics Lactobacillus reuteri Abrogates Immune Checkpoint Blockade-Associated Colitis by Inhibiting Group 3 Innate Lymphoid Cells. Front Immunol. 2019 Jun 4;10:1235. doi: 10.3389/fimmu.2019.01235. eCollection 2019.
18	Production and delivery of Helicobacter pylori NapA in Lactococcus lactis and its protective efficacy and immune modulatory activity. Sci Rep. 2018 Apr 24;8(1):6435. doi: 10.1038/s41598-018-24879-x.
19	Evaluation of type 1 immune response in naive and vaccinated animals following challenge with Leptospira borgpetersenii serovar Hardjo: involvement of WC1(+) gammadelta and CD4 T cells. Infect Immun. 2002 Nov;70(11):6147-57. doi: 10.1128/iai.70.11.6147-6157.2002.
20	Induction of Th1 cytokines by Leuconostoc mesenteroides subsp. mesenteroides (KCTC 3100) under Th2-type conditions and the requirement of NF-kappaB and p38/JNK. Cytokine. 2009 May;46(2):283-9. doi: 10.1016/j.cyto.2009.02.005. Epub 2009 Mar 18.
21	Methanobrevibacter smithii archaeosomes-entrapped mzNL4-3 virus-like particles induce specific T helper 1-oriented cellular and humoral responses against HIV-1. Curr HIV Res. 2013 Sep;11(6):491-7. doi: 10.2174/1570162x11666131216125059.
22	Mycobacterium marinum: a potential immunotherapy for Mycobacterium tuberculosis infection. Drug Des Devel Ther. 2013 Jul 29;7:669-80. doi: 10.2147/DDDT.S45197. Print 2013.
23	Immunopathological characteristics of immune reconstitution inflammatory syndrome caused by Mycobacterium parascrofulaceum infection in a patient with AIDS. Pathol Res Pract. 2011 Apr 15;207(4):262-70. doi: 10.1016/j.prp.2011.01.003. Epub 2011 Mar 4.
24	Cellular immune responses to Neisseria meningitidis in children. Infect Immun. 1999 May;67(5):2452-63.
25	Improvement of allergic dermatitis via regulation of the Th1/Th2 immune system balance by macrophages activated with lipopolysaccharide derived from Pantoea agglomerans (IP-PA1). Anticancer Res. 2009 Nov;29(11):4867-70.
26	The live attenuated Actinobacillus pleuropneumoniae triple-deletion mutant apxIC apxIIC apxIV-ORF1 strain, SLW05, Immunizes pigs against lethal challenge with Haemophilus parasuis. Clin Vaccine Immunol. 2013 Feb;20(2):134-9. doi: 10.1128/CVI.00458-12. Epub 2012 Dec 5.
27	Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2017 May;69(5):964-975. doi: 10.1002/art.40003. Epub 2017 Apr 7.
28	Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections. Vaccine. 2018 Mar 27;36(14):1893-1900. doi: 10.1016/j.vaccine.2018.02.040. Epub 2018 Mar 2.
29	A murine model of infection with Rickettsia prowazekii: implications for pathogenesis of epidemic typhus. Microbes Infect. 2007 Jun;9(7):898-906. doi: 10.1016/j.micinf.2007.03.008. Epub 2007 Mar 21.
30	Th1 epitope peptides induce protective immunity against Rickettsia rickettsii infection in C3H/HeN mice. Vaccine. 2017 Dec 18;35(51):7204-7212. doi: 10.1016/j.vaccine.2017.09.068. Epub 2017 Oct 10.
31	Salmonella Typhimurium, the major causative agent of foodborne illness inactivated by a phage lysis system provides effective protection against lethal challenge by induction of robust cell-mediated immune responses and activation of dendritic cells. Vet Res. 2017 Oct 25;48(1):66. doi: 10.1186/s13567-017-0474-x.
32	Intranasal immunization with recombinant outer membrane protein A induces protective immune response against Stenotrophomonas maltophilia infection. PLoS One. 2019 Apr 1;14(4):e0214596. doi: 10.1371/journal.pone.0214596. eCollection 2019.
33	Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6 mice infected with Streptobacillus moniliformis. Microbes Infect. 2018 Feb;20(2):101-110. doi: 10.1016/j.micinf.2017.10.001. Epub 2017 Oct 10.
34	The immune response to Trichophyton tonsurans: distinct T cell cytokine profiles to a single protein among subjects with immediate and delayed hypersensitivity. J Immunol. 1996 Dec 1;157(11):5192-7.
35	Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis. Infect Immun. 2020 Apr 20;88(5):e00081-20. doi: 10.1128/IAI.00081-20. Print 2020 Apr 20.

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