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Pathogen-host Interactions (PHI)

Yongqun "Oliver" He

        Infectious diseases remain among the most common and fatal of diseases. According to estimations of the World Health Organization, infectious diseases caused 14.7 million deaths in 2001, accounting for 26% of the total global mortality [1]. Although vaccination is effective against deadly infectious diseases, only a small number of vaccines have been successfully developed since Edward Jenner’s cowpox vaccine against smallpox was introduced more than 200 years ago. For example, Brucella melitensis causing zoonotic brucellosis has been identified more than one century ago and listed as select agents amenable for use in biological warfare and bio-terrorism; however, there is still no safe and effective Brucella vaccine available for human use [2]. New therapeutic drugs are also needed to fight against emerging drug-resistant pathogens and other pathogens. Successful development of effective vaccines and drugs relies on our better understanding of microbial pathogenesis and host protective immune mechanisms.

        Infectious disease is the result of an interactive relationship between a pathogen and its host. Pathogen-host interactions (PHI, or called host-pathogen interaction or HPI) are antagonistic relationships in which the success of each organism depends on its ability to overcome the other. Microbial virulence characterizes the relative capacity of a microbe to cause disease in host. Microbial Virulence is not only a microbial property, but it also depends on host factors as many might ignore. It can be demonstrated by the pathogenesis of avirulent microbes in immunocompromised hosts and the lack of pathogenesis of virulent pathogens in regular hosts [3]. Programmed cell death (PCD, including apoptosis, necrosis, autophagy, etc.) in pathogen-infected hosts is a direct outcome of pathogen-host interaction (PHI). Different virulent pathogens exploit different mechanisms to induce or prevent PCD to benefit their survival in the host. For example, many bacterial pathogens induce programmed apoptotic and/or necrotic cell death specifically in macrophages, but the mechanisms by which it occurs and the resulting pathology may differ [4]. The pathogenesis of Brucella spp. relies on a complex modulation of host cell death inside macrophages. Upon infection of a macrophage with Brucella, virulent Brucella prevents the macrophage from committing suicide, as programmed macrophage death would both prevent Brucella replication and expose the invading Brucella to more potent bactericidal environment outside [5]. Indeed, attenuated Brucella strains may induce necrosis in macrophages [6]. By contrast, programmed macrophage cell death is required for virulent Bacillus anthracis to spread. The ability to cause apoptosis in host macrophages is an advantage for B. anthracis, as apoptotic cells are much less likely than necrotic cells to release proinflammatory cytokines and other signals [7]. However, Salmonella apparently use macrophage cell death and the resulting inflammation to spread deeper within the host tissues [4]. In the case of virus-infected cells, the induction of early cell death would severely limit virus production and spread of progeny virus in the host. Thus, most viruses encode proteins that can inhibit apoptosis at the early stage of infection. Many viruses also induce apoptosis at late stages of infection in order to spread progeny to neighboring cells and evade host inflammatory responses [8].

        Genomic information of completely sequenced organisms provides valuable information not only for identification and reconstruction of intra-organismic processes but also for interactions between host and microbial organisms. A large amount of PHI research data is available in literature databases, and state-of-the-art microarray and proteomics approaches have created large amounts of gene expression data related to host-pathogen interactions. While lots of bioinformatics systems have been developed for genomic analysis and functional annotation in individual model organisms, different informatics tools and resources are demanded to study the intricate interactions between host and pathogen. One key research theme in He Group is integration and analysis of various PHI data with aim to better understand fundamental mechanisms in microbial pathogenesis and host immunity, allowing rational vaccine and drug design to efficiently prevent and treat infectious diseases.


  1. Becker K, Hu Y, Biller-Andorno N: Infectious diseases - a global challenge. Int J Med Microbiol 2006, 296(4-5):179-185. [PMID: 16446113]
  2. Schurig GG, Sriranganathan N, Corbel MJ: Brucellosis vaccines: past, present and future. Vet Microbiol 2002, 90(1-4):479-496. [PMID: 22303135]
  3. Casadevall A, Pirofski L: Host-pathogen interactions: the attributes of virulence. J Infect Dis 2001, 184(3):337-344. [PMID: 11443560]
  4. Navarre WW, Zychlinsky A: Pathogen-induced apoptosis of macrophages: a common end for different pathogenic strategies. Cell Microbiol 2000, 2(4):265-273. [PMID: 11207583]
  5. He Y, Reichow S, Ramamoorthy S, Ding X, Lathigra R, Craig JC, Sobral BW, Schurig GG, Sriranganathan N, Boyle SM: Brucella melitensis triggers time-dependent modulation of apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages. Infect Immun 2006, 74(9):5035-5046. [PMID: 16926395]
  6. Pei J, Ficht TA: Brucella abortus rough mutants are cytopathic for macrophages in culture. Infect Immun 2004, 72(1):440-450. [PMID: 14688125]
  7. Bergman NH, Passalacqua KD, Gaspard R, Shetron-Rama LM, Quackenbush J, Hanna PC: Murine macrophage transcriptional responses to Bacillus anthracis infection and intoxication. Infect Immun 2005, 73(2):1069-1080. [PMID: 15664951]
  8. Teodoro JG, Branton PE: Regulation of apoptosis by viral gene products. J Virol 1997, 71(3):1739-1746. [PMID: 9032302]
He Group
University of Michigan Medical School
Ann Arbor, MI 48109