Characteristics of the immunological response in the clearance of non‐typeable Haemophilus influenzae from the lung

Abstract

Summary Clearance of non-typeable Haemophilus in¯uenzae (NTHi) from the respiratory tract was investigated, over time, in immune and non-immune rats. A triphasic pattern characterized the clearance of bacteria from the lungs. Mucosal immunization enhanced bacterial clearance from the lungs in each of the three phases compared with clearance from non-immunized animals. Total clearance of bacteria was observed from lung tissue by 12 h in immune animals and 24 h in non-immune animals. Polymorphonuclear leucocytes not only arrived earlier and initially in greater numbers, but disappeared earlier in immune animals (peaking at 8 h postchallenge), compared with non-immune animals (peaking at 12 h post-challenge). Systemically derived and locally produced NTHi-speci®c IgA and IgG correlated with enhanced bacterial clearance during the secondary phase. This model demonstrates that immunized animals up-regulate and resolve in¯ammatory responses to pulmonary infection more rapidly than the non-immunized controls.

Effector Mechanisms of Protection againstPseudomonas aeruginosaKeratitis in Immunized Rats

“…The changes in the CINC-1 levels corresponded to the recruitment and resolution profiles of the PMNs. The rate of PMN recruitment in other disease settings has been associated with early bacterial clearance, such as enhanced respiratory clearance of nontypeable Haemophilus influenzae following mucosal immunization (5,10). Persistence of PMNs in the nonimmune animals during the later stages of infection may contribute to corneal scarring and perforation.…”

Efficacy of the 26-Kilodalton Outer Membrane Protein and Two P5 Fimbrin-Derived Immunogens To Induce Clearance of Nontypeable Haemophilus influenzae from the Rat Middle Ear and Lungs as Well as from the Chinchilla Middle Ear and Nasopharynx

“…Bacterial clearance was measured in the rats at 4 h postchallenge as has been described previously for this infection model (13,14). There were differences in the ability of the different LB1(f) conjugates to enhance clearance (Table 5).…”

“…Bacteria recovered in bronchoalveolar lavage fluid, middle ear lavage fluid, and lung homogenates can be measured 4 or 6 h after challenge of the lung and middle ear, respectively. Also, absolute and differential counts of white blood cells recruited to these sites can be made, the induced immunoglobulins can be isotyped, and specific cytokines produced during infection can be measured (14,15). Conversely, the chinchilla model is one of either active parenteral immunization, as described here, or can be one of passive transfer.…”

CD8+T Cells Have an Essential Role in Pulmonary Clearance of NontypeableHaemophilus influenzaefollowing Mucosal Immunization

“…

In the area of pulmonary bacterial infection it is still unclear which cells mediate the rapid upregulation and control of the inflammatory response which results in the resolution of infection and the minimization of local tissue damage (7,19,47). Classical innate immune responses involving macrophages and polymorphonuclear leukocytes (PMNs) have been seen to assist both immune and nonimmune animals in clearing infections from the lung over time.

…”

“…Classical innate immune responses involving macrophages and polymorphonuclear leukocytes (PMNs) have been seen to assist both immune and nonimmune animals in clearing infections from the lung over time. However, the cellular influx in immune animals is far greater and more rapid than in nonimmune controls (18,19). This rapid cellular response in the immune animals also corresponds to enhanced bacterial clearance and the more rapid resolution of inflammation, thus decreasing the opportunity for continued damage to local tissue.…”