The role of Langerhans cells in Pseudomonas aeruginosa infection.
OBJECTIVE
Previous experimental studies have shown that extended-wear contact lens usage results in a centripetal migration of Langerhans cells from the conjunctiva into the central cornea. To test the consequences of this, Langerhans cells were induced into the cornea before Pseudomonas aeruginosa infection in BALB/c mice that are normally resistant (the cornea heals) and in C57BL/6 mice that are susceptible (the cornea perforates) to bacterial challenge.


METHODS
Mean clinical scores, slit lamp examination, adenosine diphosphatase (ADPase), and acid phosphatase staining as well as immunostaining with DEC-205, B7-1, CD4, and interleukin-2 receptor (IL-2R) antibodies and histopathologic, RT-PCR, and delayed-type hypersensitivity (DTH) analyses were used to examine the effects on bacterial disease after polystyrene bead induction of Langerhans cells into the cornea before bacterial challenge.


RESULTS
No difference in disease response was observed in bead- versus sham-treated C57BL/6 mice after bacterial infection; however, significant differences leading to corneal perforation were seen in BALB/c mice that included an increased number of Langerhans cells in the central cornea at 1 and 6 days after infection, an increased number of B7-1+ (mature) Langerhans cells at 6 days after infection, CD4+ and IL-2R+ T cells at 5 days after infection, enhanced DTH, and increased mRNA levels for IFN-gamma in cornea and cervical lymph nodes. Alternately, levels of IL-4 were significantly higher in the cornea and cervical lymph nodes of sham- versus bead-treated animals.


CONCLUSIONS
These data provide evidence that Langerhans cells are critical in the innate immune response to P. aeruginosa and provide new information regarding the mechanisms governing resistance versus susceptibility to bacterial infection with this opportunistic pathogen.
Hazlett
Linda D
LD
Department of Anatomy/Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. lhazlett@med.wayne.edu
McClellan
Sharon A
SA
Rudner
Xiaowen L
XL
Barrett
Ronald P
RP
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D001081:Apyrase / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003315:Cornea / Q000276:immunology* / Q000473:pathology; D015818:Eye Infections, Bacterial / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007801:Langerhans Cells / Q000502:physiology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D023421:Models, Animal; D011552:Pseudomonas Infections / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D018122:B7-1 Antigen; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D000135:Acid Phosphatase; D001081:Apyrase