Kinetics of serum, tear, and corneal antibody responses in resistant and susceptible mice intracorneally infected with Pseudomonas aeruginosa

Abstract

The studies described here are aimed at determining the kinetics of antibody responses specific to Pseudomonas aeruginosa ATCC 19660 in sera, tears, and corneas of naturally resistant DBAI2 mice and susceptible C57BL16 mice after intracorneal infection. Immunoglobulin (IgG) and IgM responses in sera were significantly greater in DBA/i2 mice for the first 2 weeks postinfection. Little or no IgA was detected in the sera of mice from either strain. IgG was the predominant immunoglobulin class present in the corneas of the infected eyes from both mouse strains. However, differences in both the magnitude and the kinetics of the corneal IgG responses were noted between mouse strains. The kinetics of the corneal IgG responses were more similar to those of the serum IgG response than to those of the tear IgG response. Tear antibody responses in DBAI2 mice differed from those of C57BL/6 mice in two ways. First, there was a sharp increase in tear IgG levels 2 weeks after infection in DBA/2 mice that was not present in C57BL/6 mice. Second, IgA levels present in tears from the infected eyes of C57BU/6 mice dropped to nearly preinfection levels after the first week, whereas in DBA/2 mice, IgA levels remained elevated in the infected eyes after the first week. Determination of P. aeruginosa-specific antibody responses in the uninfected, contralateral control eyes revealed that IgA was detectable in the tears but not in the corneas of DBA/2 mice. Very little IgA was detected in the tears of the uninfected eyes of C57BU/6 mice. IgG was the only immunoglobulin class present in the uninfected corneas in both mouse strains tested. These results suggest that ocular IgA was made locally, whereas most ocular IgG may have originated from the serum, with some possible local synthesis. These immunological results indicate that DBA/2 and C57BL/6 mice respond differently to corneal challenge with P. aeruginosa.Pseudomonas aeruginosa is an opportunistic pathogen which causes severe corneal infections in humans and experimental animals (3,6,11,32,33). Previous experimental studies from our laboratory have indicated that DBA/2 mice can spontaneously restore corneal clarity within a few weeks after infection; they are therefore classified as naturally resistant (2, 12). Resistance was dependent, in part, on the presence of polymorphonuclear leukocytes, complement component C3, and the virulence of the infecting organism (7,13,16). On the other hand, C57BL/6 mice initially exhibit the same severity of ocular infection at 24 to 72 h postinfection that DBA/2 mice do but are unable to restore corneal clarity within a period of 4 weeks; they are therefore, classified as susceptible (2, 12). Studies of the inflammatory cell response during corneal infection in mice demonstrated that the polymorphonuclear leukocyte response was greater in DBA/2 mice than it was in C57BL/6 mice for the first 24 h of infection but was lower by 3 days postinfection (16a). Corneal infection in C57BL/6 mice usually leads to corneal perforation, phthisis bulbi (shrinkage...

Role of Adaptive Immunity in the Pathogenesis ofCandida albicansKeratitis

“…It was reported that after topical challenge with Pseudomonas aeruginosa, IgA was secreted locally into tears without systemic production of IgA. 17 Our data, however, that the production of IgA in splenic cells culture was also increased (Fig. 5) implied that IgA could be produced in central lymphoid organs (e.g., spleen in this case) and during corneal infection with C. albicans.…”

Aspergillus fumigatus promotes T helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells

“…Data indicated that HCEC‐derived TSLP induced a higher level of IgG but did not change the expression of IgA in the supernatant of PBMC. Preston et al also reported that IgA was not found in the serum of mouse corneas infected with Pseudomonas aeruginosa . We surmised that this phenomenon may be related to IL‐4, a potent IgG class switch factor .…”

Rapid and sensitive method for evaluating Pseudomonas aeruginosa virulence factors during corneal infections in mice

“…Immune response to infection. Previous works have established the pattern of immune responses to P. aeruginosa antigens during corneal infection with strain 19660 (20,22,23). In this study, we sought to determine whether P. aeruginosaspecific serum IgG could be elicited after infection with lowlevel challenge doses.…”

“…In this model, scratches are made on the corneas of mice anesthetized with inhalants such as ether, and the challenge strain of P. aeruginosa is applied in a small volume (5 l). However, only a few strains of P. aeruginosa have been reported to be pathogenic under these conditions, and inocula of 10 7 to 10 8 CFU are needed to initiate infection (1,2,11,15,20,22,23). The limited number of virulent strains and the need for high-challenge inocula has restricted the use of this model in the evaluation of microbial and host factors involved in the pathogenesis of P. aeruginosa corneal infections.…”