Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

Nontypeable Haemophilus influenzae (NTHi) is a commensal microbe often isolated from the upper and lower respiratory tract. This bacterial species can cause sinusitis, acute otitis media in preschool children, exacerbations in patients suffering from chronic obstructive pulmonary disease, as well as conjunctivitis and bacteremia. Since the introduction of a vaccine against H. influenzae serotype b in the 1990s, the burden of H. influenzae‐related infections has been increasingly dominated by NTHi. Understanding the ability of NTHi to cause infection is currently an expanding area of study. NTHi is able to exert differential binding to the host tissue through the use of a broad range of adhesins. NTHi survival in the host is multifaceted, that is, using virulence factors involved in complement resistance, biofilm, modified immunoglobulin responses, and, finally, formation and utilization of host proteins as a secondary strategy of increasing the adhesive ability.

Since its initial description as a Th2-cytokine antagonistic to interferon-alpha and granulocyte-macrophage colony-stimulating factor, many studies have shown various anti-inflammatory actions of interleukin-10 (IL-10), and its role in infection as a key regulator of innate immunity. Studies have shown that IL-10 induced in response to microorganisms and their products plays a central role in shaping pathogenesis. IL-10 appears to function as both sword and shield in the response to varied groups of microorganisms in its capacity to mediate protective immunity against some organisms but increase susceptibility to other infections. The nature of IL-10 as a pleiotropic modulator of host responses to microorganisms is explained, in part, by its potent and varied effects on different immune effector cells which influence antimicrobial activity. A new understanding of how microorganisms trigger IL-10 responses is emerging, along with recent discoveries of how IL-10 produced during disease might be harnessed for better protective or therapeutic strategies. In this review, we summarize studies from the past 5 years that have reported the induction of IL-10 by different classes of pathogenic microorganisms, including protozoa, nematodes, fungi, viruses and bacteria and discuss the impact of this induction on the persistence and/or clearance of microorganisms in the host.

Countless in vitro cell culture models based on the use of epithelial cell types of single lineages have been characterized and have provided insight into the mechanisms of infection for various microbial pathogens. Diverse culture models based on disease-relevant mucosal epithelial cell types derived from gastrointestinal, genitourinary, and pulmonary organ systems have delineated many key host-pathogen interactions that underlie viral, parasitic, and bacterial disease pathogenesis. An alternative to single lineage epithelial cell monoculture, which offers more flexibility and can overcome some of the limitations of epithelial cell culture models based on only single cell types, is coculture of epithelial cells with other host cell types. Various coculture models have been described, which incorporate epithelial cell types in culture combination with a wide range of other cell types including neutrophils, eosinophils, monocytes, and lymphocytes. This paper will summarize current models of epithelial cell coculture and will discuss the benefits and limitations of epithelial cell coculture for studying host-pathogen dynamics in infectious diseases.

This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.