Trachoma: protective and pathogenic ocular immune responses to Chlamydia trachomatis

Abstract

Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious blinding disease worldwide. Chronic conjunctival inflammation develops in childhood and leads to eyelid scarring and blindness in adulthood. The immune response to Ct provides only partial protection against re-infection, which can be frequent. Moreover, the immune response is central to the development of scarring pathology, leading to loss of vision. Here we review the current literature on both protective and pathological immune responses in trachoma. The resolution of Ct infection in animal models is IFNγ-dependent, involving Th1 cells, but whether this is the case in human ocular infection still needs to be confirmed. An increasing number of studies indicate that innate immune responses arising from the epithelium and other innate immune cells, along with changes in matrix metalloproteinase activity, are important in the development of tissue damage and scarring. Current trachoma control measures, which are centred on repeated mass antibiotic treatment of populations, are logistically challenging and have the potential to drive antimicrobial resistance. A trachoma vaccine would offer significant advantages. However, limited understanding of the mechanisms of both protective immunity and immunopathology to Ct remain barriers to vaccine development.

Figure 1. Clinical features and grades of trachoma.

N, normal; TF, Trachomatous inflammation–follicular; TI, Trachomatous inflammation–intense; TS, trachomatous scarring; TT, trachomatous trichiasis; CO, corneal opacity.

Figure 2. Histological section of the conjunctiva from a child with active trachoma.

A subepithelial follicle is seen. Kindly provided by Professor A. El-Asrar, King Saud University.

Figure 3. Schemas of normal conjunctiva, active trachomatous disease, and trachomatous scarring.

Figure 4. Histological sections of healthy conjunctiva and trachomatous scarring.

(Top) Healthy. (Middle and bottom) Scarred, note disruption of the epithelial and connective tissue morphology, and an increased inflammatory cells.