Table 2 Innate immunity in the human FGT

Lower genital tract (LGT) (ectocervix and vagina)	Proliferative (E2 dominant)	Secretory (P4 dominant)	References
Soluble factors (AMPs, HBD2, elafin)	↓HBD2 and elafin	↑SLPI	^{7, 23}
Epithelial cells (multilayered, squamous)	Thick vaginal epithelium	Thinner vaginal epithelium	¹⁶
Neutrophils	(=)	(=)	^{53, 59}
Macrophages	Vagina (=)	Vagina (=)	⁵⁹
NK cells (CD45+, CD56+CD3− CD16+)	(=)	(=)	^{26, 31}

Upper genital tract (UGT) (Endocervix and endometrium, fallopian tubes, and ovaries)	Proliferative (E2 dominant)	Secretory (P4 dominant)	References
Soluble factors (AMPs, HBDs, elafin)	↑HBD4 (endometrium) (note: HBD2 and elafin peak during menstruation) SLPI and elafin (fallopian tubes—constitutively expressed)	↑SLPI, HBD1, HBD3 (endometrium) (maximal expression)	^{60, 61, 62}
PRRs (TLR, NOD-1, 2)	TLR10 (fallopian tubes) TLRs 1–7 but not TLR4 (endocervix)	TLRs 2, 3 5, 6, 9, including TLR4)↑(endometrium), TLR10↑(fallopian tubes)	^{55, 63, 64, 65, 66, 67, 68}
Epithelial cells (single layer, columnar)	Thick uterine epithelium. Constitutively express IFN-ɛ (Type 1 IFN) in luminal and glandular cells highest in the proliferative phase	Thin uterine epithelium	^{16, 69}
Neutrophils	(=)	Endometrial↑	^{54, 59, 70}
Macrophages		Endometrial↑ (before menstruation)	³¹
Dendritic cells	CD83+ (=)	CD1a+↑	⁷¹
NK cells CD45+, CD56+CD3−CD16−, CD69+ CD94+	uNK ↑CTL activity	Endometrial NK cells (with NKG2D receptor) ↑MICA uNK ↓CTL activity via IL-18	^{10, 11, 12, 13, 14, 15, 26, 31, 40}

AMP, antimicrobial peptide; CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; FGT, female genital tract; HBD2, human β defensin 2; IFN, interferon; IL, interleukin; SLPI, secretory leukocyte protease inhibitor; NK, natural killer; NKG2D, an activating receptor expressed on NK cells that binds to MHC class 1 chain–related protein A and B (MICA and MICB); NOD, nucleotide-binding oligomerization domain; PRR, pattern recognition receptor; TLR, Toll-like receptor;uNK, uterine natural killer.
The effects of menstrual cycle phase (proliferative or secretory) on the levels (↑, increased; (=), constant; or ↓, decreased) and functions (activity) of innate immune cells, non-immune cells, and soluble factors.

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