At the heart of our defense against pathogens is the innate immune system, a universal and non-specific defense against infection. At the heart of innate immunity is the family of toll-like receptors (TLRs) that appear to play the primary role in recognizing the presence of pathogens and then initiating a firestorm of inflammatory and immune responses. The past decade has seen an explosion in TLR research, including their potential implication in auto-immune and chronic inflammatory diseases.

Our Special Topics ranking of the hottest TLR papers of the past decade is dominated, not surprisingly, by review articles and, in particular, those authored by Shizuo Akira and his colleagues, who in total have half a dozen of the most influential papers of the decade. Other hot papers include the seminal 1998 report by Bruce Beutler and his colleagues cloning the first TLRs and identifying them as the source of defense mechanisms against lipopolysaccharide. Other hot papers describe how different members of the TLR family identify pathogens by recognizing CpG motifs in bacterial DNA, double-stranded RNA, bacterial flagellin, and microbial lipoproteins, among others.

Over the past two years, the top 20 papers continue to be dominated by revelations on how TLR family members recognize and differentiate pathogens. Other hot papers discuss the signaling pathways and transcription factors involved in TLR initiation of inflammatory and immune responses, the potential role of TLRs in immune responses to cancer and other diseases, and the mechanisms by which the hepatitis 3 virus might evade immune responses. Finally, this listing reveals the rising interest in the RIG-1 anti-viral pathway, which works alongside TLRs to fight off infections and mediate inflammatory responses.

Methodology

To construct this database, papers were extracted based on topic-supplied keywords for Toll-Like Receptors. The keywords used were as follows: 

toll-like receptor* or TLR*

The baseline time span for this database is 1997-February 28, 2007 (first bimonthly period of 2007). The resulting database contained 7,822 (10 years) and 4,374 (2 years) papers; 24,282 authors; 81 countries; 1,040 journals; and 3,623 institutions.

Rankings

Once the database was in place, it was used to generate the lists of top 20 papers (two- and ten-year periods), authors, journals, institutions, and nations, covering a time span of 1997-February 28, 2007 (first bimonthly period of 2007, a ten-year plus two-month period).

The top 20 papers are ranked according to total cites. Rankings for author, journal, institution, and country are listed in three ways: according to total cites, total papers, and total cites/paper. The paper thresholds and corresponding percentages used to determine scientist, institution, country, and journal rankings according to total cites/paper, and total papers respectively are as follows:

Entity:	Scientists	Institutions	Countries	Journals
Thresholds:	11	59	8	13
Percentage:	1%	1%	50%	10%

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