Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies

Table 1

Lymphocyte subsets in the control of microbial infections.

Lymphocyte subset	Antigen presentation	Transcription factors	Effector molecules secreted	Mechanism	Evidence for control in intracellular infections (gene deficiency or direct involvement)
Th1	MHC class II	T-bet, STAT4, STAT1	IFN-γ, TNF-α, IL-2, lymphotoxin α	Activation of macrophages by IFN-γ, upregulation of iNOS and ROI, proliferation of CTL	IFN-γ -/- [16–21]
					TNF-α -/- [22–29]
					IL-12p40 -/- [30–32]
					IL-18 -/- [33–35]
Th2	MHC class II	GATA3, STAT5, STAT6	IL-4, IL-5, IL-9, IL-13	Stimulate B cells, antibody production, antibody class switching	Th2 cytokines [30–32]
Th17	MHC class II	RORγt, STAT3	IL-17A, IL-17F, IL-21, IL-22, CCL20	Recruitment, activation and migration of neutrophils	IL-17 -/- [36–41]
					IL-17 RA -/- [42–47]
					IFN-γ -/- [16, 18, 19, 48]
					IL-23 -/- [31, 49–51]
Tfh	MHC class II	Bcl6, c-MAF	IL-10, IL-21	Provides help for B cells to allow formation of plasma cells and memory B cells	Tfh -/- [52, 53]
					IL-21 -/- [54]
					IL-6 -/- [55]
Tregs	MHC class II	FOXP3, SMAD, STAT5	IL-10, TGF-β, IL-35	Immunosuppression and tolerance	CD4^+ Tregs [56–58]
					CD8^+ Tregs [59–61]
					IL-10 -/- [57, 62, 63]
					TGF-β -/- [64, 65]
CD8^+/CTL	MHC class I	EOMES, BLIMP1	IFN-γ, perforin, granzyme, granulysin, FAS-FAS ligand	Cytotoxicity, programmed cell death by caspase or receptor-mediated FAS-FAS ligand apoptosis	IFN-γ -/- [66–71]
					TNF-α -/- [22–28, 72]
					Perforin -/- [73–75]
					Granzyme -/- [75, 76]
γδ T	CD1c	PLZF, GATA3, TBX21	IFN-γ, IL-17A, IL-17F, IL-22	Pro- and anti-inflammatory functions at epithelial surfaces	γδ TCR -/- [77–82]
					IL-17 [37, 38, 46, 83]
					IL-22 [84]
NK	MHC class I are inhibitory	PU.1, Ets-1, GATA3, IRF-2	IFN-γ, TNF-α, perforin, granzyme, α-defensins	Cytotoxic, direct cytolysis by apoptosis, ADCC	NK -/- [85, 86]
					IFN-γ -/- [87, 88]
					Perforin -/- [87, 89]
iNKT	CD1d	PLZF, TBX21, ERK	IL-4, IFN-γ, IL-17A, GM-CSF	Pro- and anti-inflammatory functions	iNKT cells [90–95]
MAIT	MR1	ZBTB16, ROR(γt)	IFN-γ, TNF-α, IL-17, granzyme	Cytokine production, cytotoxic	MAIT -/- [96–98]
					MR -/- [99–101]
B	NA	PU.1, Pax5 Ikaros	Immunoglobulins, IL-10	Antibody secretion, neutralization, opsonization, phagocytosis, antigen presentation	B cells [102–108]
					Polymeric-Ig receptor -/- [109–113]

ADCC: antibody-dependent cellular cytotoxicity; B: B lymphocyte; Bcl6: B cell lymphoma 6; BLIMP1: PR domain zinc finger protein 1; CCL: chemokine ligand; CD: cluster of differentiation; c-MAF: c-musculoaponeurotic fibrosarcoma oncogene homolog; CTL: cytotoxic T lymphocyte; EOMES: Eomesodermin; ERK: extracellular signal-regulated kinase; Ets-1: erythroblastosis virus transcription factor-1; FOXP3: Forkhead box P3; GATA, trans-acting T cell-specific transcription factor; γδ T: gamma delta T cells; GM-CSF: granulocyte-macrophage colony-stimulating factor; IFN-γ: interferon gamma; Ig: immunoglobulin; IL: interleukin; IL-17RA: interleukin 17 receptor a; iNKT: invariant natural killer T cell; iNOS: inducible nitric oxide synthase; IRF-2: interferon regulatory factor 2; MHC: major histocompatibility complex; MR1: major histocompatibility complex class I-related gene protein; MAIT: mucosal-associated invariant T cells; NA: not applicable; NK: natural killer cells; Pax5: paired box protein 5; PLZF: promyelocytic leukemia zinc finger; RORγt: RAR-related orphan receptor gamma 2; ROI: reactive oxygen intermediates; STAT: signal transducer and activator of transcription; TBX: T-box transcription factor; Tfh: follicular helper T cells; TGF-β: transforming growth factor beta; Th: helper T cells; TNF-α: tumor necrosis factor alpha; Tregs: regulatory T cells; ZBTB16: zinc finger and BTB domain-containing protein 16.