A diverse community of trillions of commensal bacteria inhabits mucosal and epidermal surfaces in humans and plays an important role in defense against pathogens, including respiratory pathogens. Commensal bacteria act on the host's immune system to induce protective responses that prevent colonization and invasion by pathogens. On the other hand, these bacteria can directly inhibit the growth of respiratory pathogens by producing antimicrobial products/signals and competing for nutrients and adhesion sites. Such mechanisms preserve the niche for commensal bacteria and support the host in containing respiratory infections. Herein, we discuss current evidence on the role of commensal bacteria in conferring protection against respiratory pathogens and the underlying mechanisms by which these bacteria do so. A deeper knowledge of how commensal bacteria interact with the host and pathogens might provide new insights that are poised to aid in the development of vaccines and therapeutics that target infectious diseases.

Quorum sensing regulates bacterial social behaviors by production, secretion, and sensing of pheromones. In this study, we characterized a new quorum-sensing system of the Rgg/SHP class in S. pneumoniae D39. The system was found to directly induce the expression of a single gene cluster comprising the gene for the SHP pheromone and genes with putative functions in capsule synthesis. Capsule size, as measured by dextran exclusion, was increased by SHP exposure in R36A, an unencapsulated derivative of D39. In the encapsulated parent strain, overexpression of the gene cluster increased capsule size, supporting the role of Rgg/SHP in the synthesis of surface polysaccharides. Further, we found that biofilm formation on epithelial cells was reduced by overexpression of the system and increased in a mutant with an rgg deletion. Placing surface polysaccharide expression under quorum-sensing regulation may enable S. pneumoniae to tune interactions with the host and other bacteria in accordance with environmental and cell density conditions.

In this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Glued in early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150 Glued T he steps of early stage human immunodeficiency virus type 1 (HIV-1) replication include virus entry, uncoating, reverse transcription, intracytoplasmic retrograde transportation (i.e., the migration of HIV from the cytoplasmic periphery to the perinuclear space), nuclear import, and genomic integration (reviewed in reference 1). Following HIV-1 entry into the cell, viral genomic RNA and associated proteins are released into the cytoplasm as a ribonucleoprotein complex referred as the reverse transcription complex (RTC). Within the RTC, HIV-1 genomic RNA is reverse transcribed into a cDNA, which then forms a highmolecular-weight preintegration complex (PIC). HIV-1 cDNA enters the nucleus as a part of PIC by active nuclear import and subsequently integrates into the host cell genome (reviewed in reference 2).HIV-1 utilizes various cellular proteins for replication mostly by interacting with its viral proteins. Genome-wide small interfering RNA (siRNA)/short hairpin RNA (shRNA) screening as well as other functional studies have uncovered a large number of host proteins with putative roles in HIV-1 replication (reviewed in references 3, 4, and 5). Additionally, functional studies from our laboratory, as well as from other groups, have uncovered key viral and cellular protein interactions that promote successful HIV-1 nuclear import and integration (reviewed in references 2 and 6). However, molecular events associated with HIV-1 reverse transcription, uncoating, or retrograde transport in the cytoplasm are not well understood. To date, evidence suggests that gem-associated protein 2 (Gemin2) interacts with HIV-1 integrase (IN) in target cells and contributes to reverse transcription by an unknown mechanism(s) (7,8). Similarly, accumulated evidence suggests that cyclophilin A (CypA) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (prolyl isomerase Pin1) proteins interact with HIV-1 capsid (CA) protein in target cells and facilitate the proper uncoating of HIV-1 (9, 10). In addition, some other cellular factors with putative roles in HIV-1 reverse transcription and uncoating have been described in recent studies (11)(12)(13)(14). Although the exact mechanism(s) by which these cellular factors contribute to HIV-1 reverse transcription and/or uncoating is not very clear, the accumulated evidence so far clearly suggests a key role for cellular cofactors in HIV-1 uncoating and reverse transcription.Dynein adapter proteins such as dynein light chain 1 (DYNLL1, LC8, DLC1), dynein light chain Tctex-type 1 (DYNLT1), and p150Glued have been implicated in cargo recruitment to the dynein complex during retrograde transport (15-18). The dynein complex is a microtubule (MT)-associated protein c...

Recent studies suggest differential roles for CD103+ and CD11b lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11b LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two subsets. More importantly, we found, in adoptive transfer experiments, that the mice receiving CD103+ LDCs from Chlamydia-infected mice exhibited better protection than the recipients of CD11b LDCs, which was associated with more robust Th1/Th17 cytokine responses. In addition, in vitro experiments showed that CD103+ LDCs induced stronger IFN-γ and IL-17 responses, when cocutured with chlamydial antigen-primed CD4+ T cells, than CD11b LDCs. Furthermore, the blockade of PD1 in the culture of CD4+ T cells with either CD103+ or CD11b LDCs enhanced production of IFN-γ and IL-17. In conclusion, our data provide direct evidence that CD103+ LDCs are more potent in promoting Th1/Th17 immunity to chlamydial lung infection than CD11b LDCs.

Current vaccines against Streptococcus pneumoniae, a bacterial species that afflicts people by causing a wide spectrum of diseases, do not protect against all pneumococcal serotypes. Thus, alternative vaccines to fight pneumococcal infections that target common proteins are under investigation. One promising strategy is to take advantage of immune cross-reactivity between commensal and pathogenic microbes for cross-protection. In this study, we examined the antibody-mediated cross-reactivity between S. pneumoniae and Streptococcus mitis, a commensal species closely related to S. pneumoniae. Western blot analysis showed that rabbit antisera raised against S. mitis reacted with multiple proteins of virulent S. pneumoniae strains (6B, TIGR4, and D39). Rabbit anti-S. pneumoniae IgG antibodies also showed binding to S. mitis antigens. Incubation of rabbit antisera raised against S. mitis with heterologous or homologous bacterial lysates resulted in marked inhibition of the developments of bands in the Western blots. Furthermore, plasma IgG antibodies from adult human volunteers intranasally inoculated with S. pneumoniae 6B revealed enhanced S. mitis-specific IgG titers compared with the pre-inoculation samples. Using an on-chip protein microarray representing a number of selected membrane and extracellular S. pneumoniae proteins, we identified choline-binding protein D (CbpD), cell division protein (FtsH), and manganese ABC transporter or manganese-binding adhesion lipoprotein (PsaA) as common targets of the rabbit IgG antibodies raised against S. mitis or S. pneumoniae. Cumulatively, these findings provide evidence on the antibody-mediated cross-reactivity of proteins from S. mitis and S. pneumoniae, which may have implications for development of effective and wide-range pneumococcal vaccines.